[Show abstract][Hide abstract] ABSTRACT: Grafts from non-heart-beating donors (NHBDs) are used because of the limited availability of heart-beating brain-dead donors. These grafts sustain ischemic damage, and the severity of this damage varies among different areas of an organ. This study determined whether the results of islet isolation were correlated with the clinical outcomes of kidney transplantations in cases where both grafts were harvested from the same NHBD. Islets we isolated from the pancreata of 23 NHBDs between February 2004 and March 2007. Forty-six kidneys were also harvested from these NHBDs. The recipients of kidney transplants were divided into the successful isolation (n = 14) and failed isolation (n = 32) groups depending on the results of islet isolation. The clinical outcomes of kidney transplantation were compared between the recipients in these two groups. The immediate graft function rate and the 1-year graft survival rate after kidney transplantation in both groups were similar. Hemodialysis after transplantation was required for 6.0 days (SD, 5.2 days) in the successful isolation group and for 12.7 days (13.1 days) in the failed isolation group (p < 0.05). The serum creatinine concentrations at 1, 3, 6, and 12 months after transplantation were elevated in the failed isolation group (p < 0.05). The islet yield was inversely correlated with the requirement of hemodialysis (days) and the serum creatinine level at 1 month after transplantation. However, hemodialysis was required for only 7 days in the recipients of six kidneys that were obtained from NHBDs from whom <40,000 IEQ were obtained (extreme failure of islet isolation). The results of islet isolation were found to correlate with the kidney function after transplantation when both grafts are harvested from the same NHBD. However, the marginal conditions of NHBDs affect the results of islet isolation more than they do the posttransplantation kidney function.
[Show abstract][Hide abstract] ABSTRACT: 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.
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).
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.
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.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: The simultaneous transplantation of pancreas and kidney from live donors is performed in select countries. One of the reasons for this reduced applicability is the invasiveness of the donor operation. We propose the method of laparoscopic-assisted operation to be performed on live donors with minimal invasion.
The donor was placed in the right lateral decubitus position. A 7-cm upper midline incision was made, and a handport was installed in addition to two or three 12-mm ports. After the removal of the left kidney graft, the spleen and the distal part of the pancreas were completely mobilized. The splenic vein and artery were identified and mobilized. The donor was then rotated to a supine position. Dissection of the pancreatic parenchyma using ultrasound shears and ligation of the splenic vessels were performed through midline incision under direct vision. The distal part of the pancreas and the spleen were extracted.
Since December 2007, 3 donors have undergone this operation. In all 3 cases, the postoperative course was uneventful, and both the renal and pancreatic grafts functioned well.
This technique is minimally invasive and safe, and may become the standard method of live donor operation for simultaneous pancreas-kidney transplantation.
Journal of hepato-biliary-pancreatic sciences. 03/2010; 17(2):193-6.
[Show abstract][Hide abstract] ABSTRACT: Many studies have described the clinical effects of treating critical limb ischemia with granulocyte colony-stimulating factor-mobilized autologous peripheral blood mononuclear cells (M-PBMNC); however, there are no long-term data available on survival, limb salvage, or prognostic factors.
To investigate the long-term clinical outcomes of M-PBMNC implantation, we reviewed data for 162 consecutive patients with limb ischemia who were treated with M-PBMNC implantation at 6 hospitals between 2001 and 2006. A subset of 123 patients with homogenous clinical profiles was selected for prognostic factor analysis.
Of the 162 patients, 50 died during the follow-up period. The median follow-up time for surviving patients was 26.4 months. The 2-year survival rate was 65% for the 140 patients with arteriosclerosis obliterans (ASO), and 100% for the 11, 4 and 7 patients with thromboangiitis obliterans (TAO), diabetic gangrene (DG) and connective tissue disease (CTD), respectively. The 1-year amputation-free rates for ASO, TAO, DG and CTD were 70%, 79%, 75% and 83%, respectively. Common serious adverse events included heart failure (15 cases), myocardial infarction (15 cases), serious infection (13 cases), stroke (10 cases), and malignant tumor (9 cases). Significant negative prognostic factors associated with overall survival were ischemic heart disease and collection of a small number of CD34-positive cells. Factors associated with time-to-amputation and amputation-free survival were a combination of Fontaine classification and lower limb gangrene, and history of dialysis.
Collection of a small number of CD34-positive cells and ischemic heart disease were associated with a reduction in overall survival.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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%).
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.
Journal of hepato-biliary-pancreatic sciences. 08/2009; 17(2):101-7.
[Show abstract][Hide abstract] ABSTRACT: The results of clinical islet transplantation in Japan are, here in, reported and discussed its efficacy and problems.
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.
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.
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.
Journal of Hepato-Biliary-Pancreatic Surgery 02/2009; 16(2):124-30. · 1.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: For the safe operation of living donor pancreas transplantation, we investigated the utility of 11C-methionine positron emission tomography (PET) to examine the function of the residual pancreatic head in patients with pancreatic disease undergoing distal pancreatectomy and in living donors of pancreas transplantation. After 6 hours of fasting, we intravenously injected 370 to 740 MBq 11C-methionine. PET was scanned 30 minutes after injection. 11C-methionine PET uptake by the pancreatic head versus body/tail was expressed as a standardized uptake value (SUV). The SUVs of the pancreatic head were compared before versus after surgery. The SUVs of the pancreatic head in patients before and after distal pancreatectomy were 15.3 +/- 6.0 and 18.2 +/- 2.4, respectively. The SUVs of the pancreatic head in donors before and after distal pancreatectomy were 16.1 +/- 1.0 and 14.7 +/- 1.4, respectively. Both patients and donors showed no significant difference in SUVs of the pancreatic head before and after surgery. However, the SUVs of the residual pancreatic head were elevated after distal pancreatectomy in 80% of patients and 50% of donors. These data indicated that the function of the pancreatic head may be maintained or improved after distal pancreatectomy. 11C-methionine PET may become a potent modality to evaluate segmental pancreatic function for a safe living donor operation.
[Show abstract][Hide abstract] ABSTRACT: We performed 6 islet transplantations in 4 type 1 diabetes mellitus patients. From September 2003 to April 2007, 23 islet isolations were performed from pancreata of non-heart-beating donors. The pancreata preserved using a 2-layer method or simple cold storage in University of Wisconsin solution were transferred to our cell processing center. The islet isolation was performed according to the Edmonton protocol with some modifications. The immunosuppressive protocol was achieved using sirolimus, tacrolimus, and anti-CD25 antibody (basiliximab). Islet yield was 400 to 491,040 IEQ and purity was 1% to 70%. Stimulation indices upon static incubation were 1.38 to 11.69. All patients who underwent islet transplantation showed positive serum C-peptide levels immediately after transplantation. Although insulin independence was not achieved, they displayed stabilized blood glucose levels, reduced insulin doses, and disappearance of hypoglycemic unawareness. Although stomatitis and diarrhea due to the side effects of sirolimus were observed in 2 patients, there were no severe complications. In patient 1, serum C-peptide levels decreased gradually from 1 year after transplantation. In conclusion, successful islet transplantation was possible using islets isolated from the pancreata of non-heart-beating donors. Further improvements are needed to achieve prolonged graft survival.
[Show abstract][Hide abstract] ABSTRACT: We performed the first case of simultaneous pancreas and kidney transplantation from a living donor (LDSPK) in 2004. We examined the quality of life (QOL) of performed 6 recipients and 5 donors among 8 LDSPK from 2004 to 2007 at our institution using Short Form 36. All recipients achieved insulin and hemodialysis independence after LDSPK with positive serum C-peptide levels. Before LDSPK, all scores of the 8 specific domains of the recipients were low (28.2 +/- 10.6), indicating extremely poor QOL. Both the Physical and the Mental Component Summary Scores (PCS/MCS) quickly increased after LDSPK. PCS at 6, 12, and 24 months after LDSPK were significantly higher than the pretransplantation level. MCS were also significantly higher than the pretransplantation level. LDSPK showed prominent QOL improvement for the recipient. Complications were not observed in any donor. Although PCS decreased at 6 months after the operation, it recovered at 12 and at 24 months after the operation. MCS was maintained at more than 50 from 6 to 24 months after the operation. QOL was well preserved in the LDSPK donors despite the major surgery. In conclusion, LDSPK was confirmed to be a potent tool for treatment of type 1 diabetes mellitus patients with end-stage renal disease (ESRD) by complete normalization of glucose metabolism and renal function. In addition to these medical advantages, both their physical and mental QOL were improved by LDSPK.
[Show abstract][Hide abstract] ABSTRACT: ABO-incompatible kidney transplantation has become a popular alternative to kidney transplantation in Japan because of the severe shortage of cadaveric donors. In our institution, 21 cases of ABO-incompatible kidney transplantation were performed from April 2004, to October 2007. Recipient age was 42.8 +/- 14.5 years old; there were 9 men and 12 women. Duration of hemodialysis was 1,914 +/- 2,343 days. Donor operation was performed using a complete laparoscopic procedure. Recipient's splenectomy was performed using a hand-assisted laparoscopic procedure and kidney transplantation was performed with a standard method using an extraperitoneal approach. Pretransplant immunosuppressive protocol includes an administration of mycophenolate mofetil, tacrolimus, predonisolone, splenectomy, double filtration plasmapheresis (DFPP), and plasma exchange (PE). All patients showed an immediate graft function and their serum creatinine levels promptly decreased to 1.48 +/- 0.99 mg/dL on day 7 and 1.21 +/- 0.72 mg/dL on day 30. Both immunoglobulin (Ig)M and IgG titers were maintained at much lower levels for 7 days after transplantation in all patients. Cytomegalovirus antigenemia was observed in 11 patients (52.4%). One patient (4.8%) developed a Pneumocystis Carinii pneumonia and the formation of lymphocele was observed in one patient (4.8%). Total patient survival at 3 years was 95.2%, and graft survival at 3 years was 90.5%, which were almost equal to those in the patients who underwent ABO-matched, compatible kidney transplantation.
[Show abstract][Hide abstract] ABSTRACT: Reversible posterior leukoencephalopathy syndrome (RPLS) is one of the important side effects of calcineurin inhibitors (CNIs). Magnetic resonance imaging (MRI) of the brain is useful for the diagnosis of RPLS, showing the edema primarily in the cortex and subcortical white matter of the posterior brain regions. Interruption of CNIs is essential for the treatment of patients with RPLS. Herein we have described 2 cases (1.7%) of RPLS induced by CNIs after kidney transplantation. The first case was a 56-year-old man with chronic renal failure due to diabetic nephropathy who received a living-related kidney transplantation in 2006. Initial immunosuppressive therapy consisted of cyclosporine, mycophenolate mofetil (MMF), prednisolone, and basiliximab. Four months after transplantation, he developed unconsciousness and paralysis. The second case was a 24-year-old woman with end-stage renal disease due to Alport syndrome who received an ABO-incompatible living-related kidney transplantation. Initial immunosuppressive therapy consisted of tacrolimus, MMF, prednisolone, and basiliximab. On postoperative day 3, she developed convulsions and unconsciousness. In both patients, RPLS was diagnosed with neurological symptoms and MRI findings at early stage of the disease, and they recovered rapidly from the disease by the interruption of CNIs. Our data demonstrated that early diagnosis and immediate interruption of CNIs were essential for the treatment of RPLS after kidney transplantation.
[Show abstract][Hide abstract] ABSTRACT: The patient was a 53-year-old male with Stage IV gastric cancer with Virchow's lymph node and para-aorta lymph node metastasis. The chemotherapy regimen was given S-1 orally at 80 mg/m(2) day on day 1 to 21 and CDDP intravenously at 60 mg/m(2) day on day 8, repeated for 35 days. After two courses and a reduced regimen with S-1 64 mg/m(2) day plus CDDP 35 mg/m(2) day, the tumor lesion became CR and the serum CEA 575 ng/mL level before therapy decreased to the normal level. The patient received six courses of oral S-1(64 mg/m(2) day)for 28 days followed by a 14- day rest as maintenance therapy. The serum CEA elevated 13 months after the treatment, and the patient received a reduced course and two-course S-1/CDDP therapy. The serum CEA decreased to normal level and the patient has now survived 1 year 5 months without recurrence.
Gan to kagaku ryoho. Cancer & chemotherapy 09/2008; 35(8):1387-90.
[Show abstract][Hide abstract] ABSTRACT: 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.