Effectiveness of Preceding Solo Kidney Transplantation for Type 1 Diabetes With End-Stage Renal Failure.

Preceding solo kidney transplantation for type 1 diabetes with end-stage renal failure is controversial because of less pancreatic graft survival in pancreas transplantation after kidney transplantation (PAK) than in simultaneous pancreas and kidney transplantation (SPK). METHODS: To study the effectiveness of preceding solo kidney transplantation for type 1 diabetes with end-stage renal failure, comparative retrospective analysis was performed between SPK (n = 232) and PAK (n = 39) that were performed until December 2016. RESULTS: At 1, 3, and 5 years, pancreatic graft survival in SPK was 87.5%, 86.4%, and 82.8%, respectively, and 87.1%, 65.0%, and 49.1%, respectively, in PAK, which showed lesser long-term graft survival than SPK. Because 10 cases out of 16 (62.5%) failed into pancreatic graft loss with rejection in PAK, which was about 3 times more than in SPK, control of rejection is very important; rejection episodes were decreased by rabbit antithymocyte globulin induction resulting in improved graft survival. Five-year patient survival was 88.0% in SPK and 96.6% in PAK. CONCLUSION: Considering patient survival, preceding solo kidney transplantation for type 1 diabetes with end-stage renal failure should be performed if a donor is available.

Gene Expression Profiling of Peripheral Blood From Kidney Transplant Recipients for the Early Detection of Digestive System Cancer.

BACKGROUND: Kidney transplant recipients are at increased risk of developing cancer in comparison with the general population. To effectively manage post-transplantation malignancies, it is essential to proactively monitor patients. A long-term intensive screening program was associated with a reduced incidence of cancer after transplantation. This study evaluated the usefulness of the gene expression profiling of peripheral blood samples obtained from kidney transplant patients and adopted a screening test for detecting cancer of the digestive system (gastric, colon, pancreas, and biliary tract). STUDY DESIGN AND METHOD: Nineteen patients were included in this study and a total of 53 gene expression screening tests were performed. The gene expression profiles of blood-delivered total RNA and whole genome human gene expression profiles were obtained. We investigated the expression levels of 2665 genes associated with digestive cancers and counted the number of genes in which expression was altered. A hierarchical clustering analysis was also performed. The final prediction of the cancer possibility was determined according to an algorithm. RESULTS: The number of genes in which expression was altered was significantly increased in the kidney transplant recipients in comparison with the general population (1091 ± 63 vs 823 ± 94; P = .0024). The number of genes with altered expression decreased after the induction of mechanistic target of rapamycin (mTOR) inhibitor (1484 ± 227 vs 883 ± 154; P = .0439). No cases of possible digestive cancer were detected in this study period. CONCLUSION: The gene expression profiling of peripheral blood samples may be a useful and noninvasive diagnostic tool that allows for the early detection of cancer of the digestive system.

Kidney Transplantation, Cardiovascular Risk, and Long-Term Dialysis in Japan.

BACKGROUND: The waiting time for deceased-donor kidney-only transplantations in Japan is long. Herein, we assessed the effect of length of dialysis on the outcomes of these patients. METHODS: We divided patients into 2 groups based on length of dialysis (Group A, <15 years, and Group B, ≥15 years), and compared the background and outcomes after kidney transplantation. RESULTS: Group A included 210 patients and Group B included 35 patients. In Group B, 20% of transplants were from living donors. Patient age (P = .017) and the hepatitis C infection rate (P = .018) were significantly higher in Group B, whereas hypertension (P = .011), diabetes (P = .041), and ABO-incompatibility rates (P = .015) were significantly higher in Group A. The 5- and 10-year survival rates were 97.0% and 95.4%, respectively, in Group A and 97.1% and 97.1%, respectively, in Group B. The 5- and 10-year graft survival rates were 95.4% and 84.8%, respectively, in Group A and 97.1% and 73.1%, respectively, in Group B. There were no significant differences between the groups in patient survival (P = .74) and graft survival (P = .72). The 5- and 10-year cardiovascular event-free survival rates were 95.9% and 92.4%, respectively, in Group A and 88.6% and 76.8%, respectively, in Group B. Cardiovascular event-free survival was significantly higher in Group A (P = .038). Cox stepwise multivariate analysis indicated that length of dialysis was a significant predictor of cardiovascular events (hazard risk, 1.007; range, 1.001-1.012; P = .012). CONCLUSION: The prognosis after kidney transplantation is promising even after a long length of dialysis, although evaluation of the cardiovascular risk is needed in these cases.

Positron Emission Tomography and Autoradiography of (18)F-Fluorodeoxyglucose Labeled Islets With or Without Warm Ischemic Stress in Portal Transplanted Rats.

OBJECTIVE: The use of positron-emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) -labeled islets has been considered to be a potential modality to visualize and quantify early engraftment of islet transplantation. The objective of this study was to evaluate the early islets' survival of the FDG-labeled islets with or without warm ischemic stress in portal transplanted rats using PET and autoradiography. METHODS: Islets were isolated from Lewis rat pancreata with or without 30-minute warm ischemia times (WITs). For islets' labeling, 300 islets were incubated with 3 MBq FDG for 60 minutes. FDG-labeled islets were transplanted into the liver via portal vein. In in vivo study, a PET study was scanned for 90 minutes and the FDG uptake was expressed as percentage of liver injection dose (ID). In ex vivo study, the liver was exposed for 30 minutes with single fluorescence autoradiography. RESULTS: In the PET study, the percentage of liver ID of the islets without WIT was 27.8 and that of the WIT islets was 20.1 at the end of islet transplantation. At 90 minutes after transplantation, the percentage of liver ID was decreased to 14.7 in the islets without WIT and 10.1 in the WIT islets. In the autoradiogram, the number of hot spots was more obviously visualized in the liver transplanted without WIT islets than in the liver transplanted with WIT islets. CONCLUSION: Almost 50% of the islets were immediately lost in both the islets without WIT and those with WIT transplantation in the early period. However, islet survival was 1.4 times higher in the islets without WIT than that in those with WIT in the early engraftment phase.

Initial experience with a tailor-made simulation and navigation program using a 3-D printer model of kidney transplantation surgery.

INTRODUCTION: Three-dimensional (3-D) printing systems allow for the creation of surgical models mimicking real tissue. We developed a kidney graft and pelvic cavity replica as a patient-specific 3-D model using a 3-D printing system with simultaneous jetting of different materials and subsequently evaluated the usefulness of surgical simulation and navigation of living kidney transplantation. METHODS: After generating a stereolithographic file of the organ surface based on multidetector computed tomographic data, we created a 3-D organ model using an inkjet 3-D printer and manufactured a pelvic cavity replica using patient-specific data. RESULTS: The patients' individual 3-D printed models were used to plan and guide the surgical procedures for laparoscopic donor nephrectomy and recipient transplantation surgery. The 3-D organ replicas obtained using transparent materials allowed for the creation of models that showed the visceral organs, blood vessels, and other details, thereby overcoming the limitations of conventional image-guided navigation. Our pelvic replicas can be made according to each patient's specific anatomical data, thus representing personalized surgical procedures. This level of detail of the anatomy enables the surgeons and trainees to virtually treat various pelvic conditions before they perform the surgical procedure. The use of these replicas may also reduce the length of the operation and provide better anatomical reference tools for tailor-made simulation and navigation of kidney transplantation surgery, consequently helping to improve training for the operating room staff, students, and trainees. CONCLUSIONS: We believe that our sophisticated personalized donor graft and pelvic replications obtained using a 3-D printing system are advantageous for kidney transplantation surgery.

A novel screening test for detecting graft thrombosis after pancreatic transplantation using contrast-enhanced ultrasonography with sonazoid.

Pancreatic graft thrombosis is the primary cause of nonimmunologic graft loss, with an incidence ranging from 5% to 15%. Therefore, developing a screening test to detect graft thrombosis after pancreatic transplantation is important. We created a screening test to assess graft thrombosis after pancreatic transplantation using contrast-enhanced ultrasonography (CEUS) with Sonazoid in addition to Doppler ultrasonography. A total of seven patients were examined using CEUS after undergoing pancreatic transplantation. All patients were observed to have a clear blood flow from the horizontal region to the peripheral region of the splenic vein in the pancreatic graft, and only one of the seven patients exhibited a blood flow in the horizontal portion of the splenic vein on Doppler ultrasonography performed immediately after pancreatic transplantation. Results from CEUS with Sonazoid showed the blood flow in the splenic vein and parenchyma of the pancreatic graft in detail, despite the slow and lateral blood flow in the splenic vein of the pancreatic graft immediately after transplantation.

Long-term outcomes of clinical transplantation of pancreatic islets with uncontrolled donors after cardiac death: a multicenter experience in Japan.

BACKGROUND: Pancreatic islet transplantation has emerged as an effective treatment for type 1 diabetes mellitus, but its use is limited due to an insufficient supply of cadaveric pancreata. In Japan, uncontrolled donors after cardiac death (DCD) are not deemed to be suitable for whole-organ pancreatic transplantation, and can provide a source of pancreas for islet transplantation. However, the long-term outcomes and utility of uncontrolled DCD in the clinical setting remain controversial. Here, we summarize the long-term outcomes of islet transplantation employing uncontrolled DCD as reported to the Japan Islet Transplantation Registry. METHODS: Sixty-four isolations and 34 transplantations of pancreatic islets were conducted in 18 subjects with type 1 diabetes mellitus under the cover of immunosuppression with basiliximab, sirolimus, and tacrolimus. All donors were uncontrolled DCD at the time of harvesting. The mean follow-up time was 76 months. RESULTS: Of the 18 recipients, 8, 4, and 6 recipients received 1, 2, and 3 islet infusions, respectively. Overall graft survivals (defined as a C-peptide level ≥0.3 ng/mL) were 72.2%, 44.4%, and 22.2% at 1, 2, and 5 years, respectively, whereas the corresponding graft survivals after multiple infusions were 90.0%, 70.0%, and 30.0%, respectively. Three of these recipients achieved insulin independence in 14, 79, and 215 days. HbA1c levels and the requirement of exogenous insulin were improved before loss of graft function. All recipients became free of severe hypoglycemia unawareness, however, at least 5 of 14 patients who had graft failure experienced recurrence of severe hypoglycemia after the loss of graft function. CONCLUSIONS: Islet transplantation from DCD can relieve glucose instability and problems with hypoglycemia when the graft is functioning. However, islets from uncontrolled DCD may be associated with reduced long-term graft survival. Further improvements in the clinical outcome by modification of islet isolation/transplantation protocols are necessary to establish islet transplantation using DCD.

Organ donation from brain-dead and circulatory-dead donors: single-institution experiences.

Although the number of organ donations is extremely small in Japan, organ donation from brain dead (DBD) donors is increasing since the revised Law for Organ Transplantation was enacted on July 17, 2010. In our institution, organ donations had so far been performed from 247 donors (DCD 242, DBD 5), which is the largest number in Japan. In this study, we analyzed the status of organ donation before and after the enforcement of the revised law. After the enforcement of the revised law, the option of organ donation was shown to the more families of potential donors by the doctors or donor coordinators. However, the final number of donors was almost the same. The frequency of DBD donors of all donors increased (33.3%) as compared to 9.1% before the enforcement of the revised law. Reasons for rejection of donation from donor families were mainly based on the lack of understanding of brain death. To increase organ donation, we should promote social recognition of brain death, having the Organ Donation Card, and discussion of organ donation in each family.

Establishment of educational program for multiorgan procurement from deceased donors.

INTRODUCTION: Multiorgan procurement is not an easy procedure and requires special technique and training. Since sufficient donors are not available for on-site training in Japan, establishment of the educational program for multiorgan procurement is mandatory. MATERIALS AND METHODS: Development of e-learning and simulation using pigs are our main goals. E-learning contains three dimensional computer graphic (3DCG) animations of the multiorgan procurement, explanation of both donor criteria and procurement procedure, and self-assessment examination. To clarify the donor criteria, the risk factors to 3-month survival of the recipients were analyzed in 138 adult cases of liver transplantation. The 3DCG animation for liver procurement was developed, which was used in the lecture prior to the simulation on August 10, 2013. The results of the examination after this lecture (exam 2013) were compared with the results after the lecture without using animation in 2012 (exam 2012). The simulation was performed by 97 trainees divided into 9 teams, and the surveys were conducted. RESULTS: The risk factors for early outcome of the recipients were cold ischemia time (≥ 10 hours), Model for End-stage Liver Disease score (≥ 20), and donor age (≥ 55 years). Results of examination showed that overall percentage of the correct answers was significantly higher in exam 2013 than in exam 2012 (48.3% vs 32.7%; P = .0001). The survey after the simulation of multiorgan procurement revealed that most trainees thought that the simulation was useful and should be continued. CONCLUSION: The novel educational program could allow young surgeons to make precise assessments and perform the exact procedure in the multiorgan procurement.

Three-dimensional computed tomographic volumetric changes in pancreas before and after living donor surgery for pancreas transplantation: effect of volume on glucose metabolism.

In the present study, we aimed to compare the pancreas volumetric changes before and after living donor surgery for pancreas transplantation, using three-dimensional (3D) computed tomography (CT) and glucose metabolism. Pancreatic volume (PV) measurement using 3D CT was performed in 13 consecutive donors who underwent distal pancreatectomy for simultaneous living donor pancreas and kidney transplantation. PV was measured using a workstation before and 3 months after living donor operation. As the parameters of glucose metabolism, hemoglobin A1c (HbA1c) level, fasting plasma glucose (FPG) level, body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), and insulinogenic index (IGI) were examined simultaneously with the PV measurement. The preoperative and postoperative PVs of pancreas was 30 ± 5 mL and 42 ± 9 mL, respectively. The postoperative PV was significantly higher than the preoperative PV (P < .01) and increased by approximately 40% at 3 months after surgery. The postoperative FPG and HbA1c levels were significantly higher than the preoperative values (P < .01). BMI decreased significantly after surgery (P < .01). No differences in HOMA-IR and IGI were noted between before and after surgery. Diabetes mellitus was not observed any of the 13 living donors during this period. Distal pancreatectomy for living donors caused an increase in the PV and maintained insulin resistance, but it was not sufficient to maintain glucose metabolism at the preoperative state.

Utility of glucagon stimulation test in type 1 diabetes after pancreas transplantation.

BACKGROUND: Despite recent progress of immunosuppressive therapy with newly developed agents, long-term pancreatic graft survival after pancreas transplantation still remains low. Therefore, precise assessment of ß-cell function after pancreas transplantation is necessary. METHODS: Pancreatic ß-cell secretory activity was measured by means of the peripheral plasma fasting serum C-peptide (CPR) response to 1 mg of glucagon intravenously in 23 patients after pancreas transplantation. The utility of ΔCPR after injection was compared with other indices that reflect insulin secretion. RESULTS: When we performed the test, 6 patients still needed insulin injection after the transplantation. Mean CPR before and after glucagon intravenously were 1.9 ± 0.98 ng/mL and 4.6 ± 2.29 ng/mL, respectively. Fasting serum CPR, secretory unit of islet in transplantation (SUIT) index, and ΔCPR after glucagon injection were significantly different between insulin users and nonusers. During follow-up (501 ± 228 days), 3 patients could stop using insulin, and their increase of CPR (1.8 ± 0.5 ng/mL) was significantly higher than that in continuous insulin users (0.3 ± 0.3 ng/mL). CONCLUSION: Fasting CPR, SUIT index, and ΔCPR after glucagon injection could reflect ß-cell function for post-pancreas transplant patients, and glucagon stimulation test could give us additional information to predict insulin-free treatment.

Single-institution outcomes in the first year of pancreas transplantation from brain-dead donors.

BACKGROUND: Under a revision to the law in 2010, the number of pancreas transplantations from brain-dead donors has been increasing in Japan. We started a new Pancreatic Transplant Program at Fujita Health University Hospital in September 2012. METHODS: A total of 11 cases of pancreas transplantation from brain-dead donors performed at Fujita Health University Hospital were analyzed in terms of the background characteristics of the donors and recipients and the outcomes. RESULTS: The mean age of the recipients was 45.2 years, and all recipients had a long-term history of diabetes (mean: 32.5 years). In the simultaneous pancreas and kidney transplantation (SPK) cases, the patients also had a long history of hemodialysis (mean: 8.0 years). Although the average donor age was 42.5 years, 90% of the donors were marginal donors, defined according to the following factors: (1) >45 years old, (2) death from cardiovascular disease, (3) episodes of cardiac arrest, (4) use of high doses of catecholamines. The pancreatic graft survival rate was 100%, although 1 patient required a small amount of insulin to maintain euglycemia. In addition, the kidney graft survival rate was also 100% in the SPK cases. CONCLUSIONS: The new Pancreatic Transplant Program at Fujita Health University has provided excellent outcomes for type 1 diabetic patients.

Study of transforming growth factor-ß1 gene, mRNA, and protein in Japanese renal transplant recipients.

BACKGROUND: Transforming growth factor (TGF)-ß1 may contribute to chronic allograft nephropathy and graft loss; however, the exact molecular mechanism remains unclear. Therefore, we assess the relationship between TGF-ß1 gene polymorphisms, expression, and development of allograft nephropathy. METHODS: We studied 135 renal transplant recipients at our hospital. TGF-ß1 gene polymorphisms (codons 10 and 25) were determined from peripheral blood leukocyte DNA. Plasma TGF-ß1 mRNA was measured by real-time polymerase chain reaction and TGF-ß1 protein levels were assessed by enzyme-linked immunosorbent assay. The relationship between TGF-ß1 genotyping, expression, and rejection and results of renal biopsy were evaluated. RESULTS: The genotype frequency of transplant recipients was 49.6%, 30.4%, and 20.0% for C/T, C/C and T/T at codon 10, 100% for G/G at codon 25, respectively. According to the criteria of Banff '97 classification, 24 cases were classified as acute rejection and whose genotypes were 16, 3, and 5 cases for C/T, C/C and T/T at codon 10. Plasma mRNA expression was elevated in 14 cases and decreased in 8 cases after acute rejection. We measured 267 specimens of TGF-ß1 protein and there was no relation between amount of TGF-ß1 protein and mRNA. CONCLUSION: Our results suggest that the relationship between plasma TGF-ß1 expression and the development of allograft nephropathy remains uncertain. Frequency of allograft rejection differ with TGF-ß1 codon 10 genotypes and the high-risk genotype was different from the reports of other countries.

Association of DNA amplification with progress of BK polyomavirus infection and nephropathy in renal transplant recipients.

PURPOSE: BK polyomavirus-associated nephropathy (BKVAN) is an important cause of renal allograft loss. Immunosuppression therapy in renal transplant recipients can lead to the reactivation of latent BK polyomavirus (BKV) infection, leading to BK viruria and viremia. This single-center study aimed to clarify the association between quantitative measurement of BKV DNA and the progression of BKV infection, and secondly to identify the risk factors associated with the evolution of viruria to viremia. METHODS: We retrospectively analyzed 266 patients who underwent renal transplantation in our center from October 2006 to February 2013. We examined the viral loads of BKV in urine and plasma by quantitative real-time polymerase chain reaction assay after screening all of the recipients by urinary sediment examination. BKVAN was diagnosed by histological examination with immunohistochemistry of the large T antigen in biopsy specimens. RESULTS: Overall, 22 recipients showed BK viruria alone, whereas 22 progressed to BK viremia, of which 6 patients were diagnosed with BKVAN. Among BKVAN patients, 2 cases progressed to graft loss at 59 months and 31 months after diagnosis, respectively. In BKVAN group, the plasma viral loads were significantly higher than those in viremia without nephropathy (P < .001). Multivariate analysis revealed that the evolution of viruria to viremia was associated with recipient age over 55 years (odds ratio, 32.08; 95% confidence interval, 2.1-489.5) and tacrolimus exposure (odds ratio, 11.98; 95% confidence interval, 1.34-107.04). CONCLUSIONS: The progression from viremia to BKVAN was strongly associated with increasing plasma viral loads for BKV DNA. The cutoff value of 1 × 10(4) copies/mL for plasma viral loads could differentiate between BKVAN and viremia alone. Further, recipient age over 55 years and tacrolimus exposure were independently associated with the evolution of viruria to viremia.

Pathologic findings of renal biopsy were a helpful diagnostic clue of stenosis of the iliac segment proximal to the transplant renal artery: a case report.

Common iliac artery stenosis after renal transplantation is a rare complication; it can occur in the course of hypertension and renal dysfunction. We report a case of suspected renal allograft rejection with iliac artery stenosis proximal to a transplanted kidney. A 52-year-old man with a history of cadaveric kidney transplantation 26 years previously underwent a second cadaveric kidney transplantation in the left iliac fossa because of graft failure 3 years before. In June 2012, the patient had progressive renal dysfunction. In July, a percutaneous needle biopsy was taken, and it showed no rejection; however, his renal function continued to get worse through September. A percutaneous allograft renal biopsy was performed under ultrasound guidance and showed hyperplasia of the juxtaglomerular apparatus and renin granules. Magnetic resonance angiography was used to evaluate the arteries in the pelvis and showed left common iliac artery stenosis, and a stent was placed. After percutaneous intervention, the patient's ankle brachial pressure index was within the normal range and the allograft function had improved.

Changes in quality of life in deceased versus living-donor kidney transplantations.

OBJECTIVE: In Japan, >80% of kidney transplantations (KTs) are performed from living donors because of a severe shortage of deceased donors. Moreover, >90% of deceased donors are non-heart-beating donors. In this study, we compared the quality of life (QOL) of the recipients between living- and deceased-donor KT performed in our hospital. METHODS: QOLs of 91 recipients (11 deceased donors and 80 living donors) were analyzed using the Short Form 36 before and 1, 2, and 3 years after KT. Changes in QOLs were compared between deceased-donor KT (group DD) and living-donor KT (group LD). RESULTS: In group DD, physical (PCS) and mental (MCS) component summary scores before transplantation were 43.7 and 48.7, respectively. PCS decreased to 35.3 at 1 year and 34.2 at 2 years, but increased to 52.6 at 3 years. MCS as 43.2 at 1 year, 52.2 at 2 years, and 44.5 at 3 years. In group LD, PCS and MCS before transplantation were 36.9 and 42.6, respectively. PCS increased to 43.3 at 1 year, 47.6 at 2 years, and 51.0 at 3 years, and MCS increased to 47.8 at 1 year, 50.1 at 2 years, and 49.6 at 3 years. CONCLUSIONS: The recipients of living-donor KT showed an improvement of QOL immediately after transplantation. However, in the recipients of deceased-donor KT, physical QOL (PCS) decreased for 2 years after transplantation. The reasons seem to be long waiting period and the use of non-heart-beating donors in deceased-donor KT in Japan.

A case of Ramsay Hunt syndrome in living-kidney transplant recipient.

A 36-year-old woman underwent ABO-incompatible living-donor kidney transplantation. Immunosuppression was achieved by quadruple therapy with tacrolimus, basiliximab, mycophenolate mofetil (MMF), and prednisone. Desensitization and removal of anti-ABO antibody was achieved by administration of MMF for 4 weeks before transplantation followed by intravenous administration of rituximab, double-filtered plasmapheresis, and plasma exchange. At 1 month after transplantation, she complained of left ear pain without vesicle rash, tinnitus, and vertigo. Physical examination revealed left facial paralysis and nystagmus. T2 fluid-attenuated inversion recovery magnetic resonance imaging (MRI) visualized swelling of the left facial nerve. Real-time polymerase chain reaction showed the existence of varicella zoster virus DNA in the patient's tears and saliva. The final diagnosis was Ramsay Hunt syndrome without vesicle rash, which is called zoster sine herpete. The patient was treated by intravenous administration of acyclovir (3 mg/kg, 3 times per day) in addition to the reduction of the MMF dose. For facial nerve palsy, prednisolone was prescribed for 3 days and then gradually tapered. These treatments improved the symptoms of tinnitus and vertigo after a month; the facial nerve palsy completely disappeared after 10 months. This case demonstrated MRI to be a useful modality for the early diagnosis of Ramsay Hunt syndrome without vesicle eruption.

Evaluation of segmental pancreatic function using 11C-methionine positron emission tomography for safe living donor operation of pancreas transplantation.

For a safe living pancreas donoration for transplantation, we evaluated the function of the residual pancreas head using 11C-methionine positron emission tomography (PET) in 13 cases before and after distal pancreatectomy. After 6 hours of fasting, we intravenously administered 11C-methionine (370 to 740 MBq), performing PET at 30 minutes thereafter. 11C-methionine PET uptake in the pancreas head was expressed as a standardized uptake value (SUV) for comparison before versus after surgery: 17.3 ± 2.5 versus 17.4 ± 4.9, respectively, demonstrating no significant difference. However, the changes in SUVs of the residual pancreas head showed three patterns after surgery. The SUVs were elevated in three donors after surgery, hypermetabolite type; maintained in five donors, normometabolite type; and decreased in five donors hypometabolite type. The percentages of subjects with a postoperative HbA1c value more than 5.8%, the upper normal limit, were 33% in hypermetabolite type; 40% in the normometabolite type; and 60% in the hypometabolite type. Although diabetes mellitus has not developed in any of the 13 donors, the pancreatic head function after distal pancreatectomy was slightly decreased, especially among the hypometabolite type. To avoid postoperative diabetes mellitus for a prolonged period, donors who show decreased SUVs after surgery should be strictly followed. In conclusion, 11C-methionine PET may be a potent modality to evaluate segmental pancreatic function for a safe living donor pancreatectomy.

Actions of the Japanese Pancreas and Islet Transplantation Association regarding transplanted human islets isolated using Liberase HI.

PURPOSE: The potential for introducing transmissible spongiform encephalopathy (TSE) into islet cells was indicated by recognizing that Liberase HI is isolated from Clostridium histolyticum grown in media containing brain-heart infusion broth. A national team within the Japanese Pancreas and Islet Transplantation Association implemented an islet transplantation program in Japan using Liberase HI. The program comprised 65 islet isolations from non-heart-beating donors and 34 transplants into 18 patients. Herein, we have summarized how the Association followed these recipients over the long term. PROCEDURES: We established an ad hoc committee to follow recipients transplanted with islets isolated using Liberase HI after becoming informed of the associated dangers of using this enzyme. We also stopped islet transplantations using Liberase. The committee addressed the major concerns of the risk of the collagenase being contaminated with TSE and of the recipient follow-up. All recipients were examined by diffusion MRI and EEG and then scheduled for evaluation and follow-up by specialists in Creutzfeldt-Jakob disease (CJD). Bioassays of bovine spongiform encephalopathy prions in the enzyme proceeded using knock-in mice expressing bovine prion protein. These assays could detect contaminating prions at a dilution of 1 × 10(4). After inactivating its collagenase activity, Liberase HI was injected into the abdominal cavities of knock-in mice. Four months later, prion infectivity in Liberase HI was evaluated by immunohistochemical staining and Western blotting of spleen homogenates using anti-prion protein antibodies. MAIN FINDINGS: Western blotting and immunohistochemical staining did not detect prions in Liberase HI. Diffusion MRI and EEG evaluations performed by CJD specialists confirmed that none of the transplanted recipients had CJD. CONCLUSIONS: Three years of follow-up revealed that none of the Japanese recipients of islet transplants developed CJD. Prion bioassays showed that the Liberase HI used to isolate islets for transplantation was free of infectious TSE prions.

Living related pancreas transplantation alone with enteric drainage in Japan: case report.

In this study, we report a living donor partial pancreas transplantation using intraportal donor-specific leukocyte transfusion (DSLT). The recipient was a 38-year-old woman who had type I diabetes mellitus for 17 years. Hypoglycemia occurred 2 or 3 times per week. Her hemoglobin A1c level was 9.0%, and she required 70 U of insulin almost every day. The donor was her 64-year-old father. The steroid-minimized immunosuppressive protocol included 1.5mg of thymoglobulin administered with a steroid bolus on days 0, 4, and 7 postoperatively. Steroids were never prescribed thereafter. Postoperative maintenance therapy included tacrolimus (FK506) and mycophenolate mofetil. In addition to these conventional approarches, we administered intraportal DSLT on days 0, 1, 4, and 7 after transplantation. The donor-specific leukocytes (40mL) had been separated from donor whole blood using an apheresis filter (Cellsorba EX; Asahi Kasei medical Co, Ltd, Tokyo, Japan). In the recipient operation, a segmental pancreas graft was transplanted into the right iliac cavity with enteric drainage with a pancreatic duct stent. Operation time was 6 hours. The postoperative course was uneventful. The patient was discharged on day 15 after transplantation. There was no acute rejection for six months after transplantation. The hemoglobin A1c level recovered to 5.1% with 6 U of insulin per day. At immunologic analysis, only interleukine-10 cytokine production was elevated at 7 days after transplantation. At flow cytometry cross-match analysis, the immunoglobulin M antibody decreased from day 7 after transplantation. We conclude that intraportal DSLT may be an effective adjunct to a steroid-free regimen.