Chikara Iwashita

Resection of the inferior head of the pancreas: report of a case.

We developed a new technique for partial resection of the head of the pancreas with an end-to-side pancreaticoduodenostomy, while preserving the duodenum, the common bile duct, and the upper part of the head of the pancreas around the duct of Santorini. A resection of the inferior head of the pancreas was performed in a patient with an intraductal mucin-producing tumor of the pancreas. This procedure is considered to be appropriate for treating both benign disease and noninvasive malignant disease involving either the uncinate process or the duct of Wirsung, because it removes both the uncinate process and the pancreatic tissue around the duct of Wirsung. We thus believe that a resection of the inferior head of the pancreas with an end-to-side pancreaticoduodenostomy can help play a significant role in the management of patients with benign diseases and localized malignant tumors of the pancreas.

Living donor pancreas transplantation in Japan

Background/purposeLiving-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.MethodsTwelve 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.ResultsNo 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%).ConclusionsBased 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.

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.

Two Cases of Calcineurin Inhibitor-Associated Reversible Posterior Leukoencephalopathy Syndrome in Renal Transplant Recipients

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.

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.

Laparoscopic‐assisted distal pancreatectomy and nephrectomy from a live donor

BackgroundThe 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.MethodThe 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.ResultsSince 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.ConclusionThis technique is minimally invasive and safe, and may become the standard method of live donor operation for simultaneous pancreas–kidney transplantation.

Evaluation of Segmental Pancreatic Function Using 11C-Methionine Positron Emission Tomography for Safe Operation of Living Donor Pancreas Transplantation

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.

Successful Islet Transplantation From the Pancreata of Non-Heart-Beating Donors

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.

Results of kidney transplantation from ABO-incompatible living donors in a single institution.

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. Recipients 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.

Evaluation of pancreatic function in normal pancreas as living-related donors and type 1 diabetic pancreas as recipients for pancreas transplantation using 11c-methionine positron emission tomography.

To the Editor: L iving-donor pancreas transplantation has been developed as one of the effective therapeuticmodalities for patientswith type 1 diabetes. The safety to the donor is a major consideration in this procedure. The donor pancreatic endocrine function has been widely evaluated using both oral and intravenous glucose tolerance tests. Although these tests are useful for evaluation of the endocrine function of the entire organ, they cannot be used to evaluate the segmental pancreatic function. On the other hand, positron emission tomography (PET) can be used to evaluate the segmental pancreatic function, such as the functions of the remnant pancreas head after the donor operation and the pancreas body/tail as a graft for living-related pancreas transplantation. The C-methionine (MET) uptake of the pancreas is correlated not only with acinar cell functions, such as the amylase output, but alsowith the duct cell functions, such as the pancreatic juice bicarbonate concentration and volume. Furthermore, the METuptake was related to the insulinogenic index, which is one of the pancreatic endocrine function tests. Kono et al demonstrated operative preservation of pancreatic function, including exocrine and endocrine functions, by MET-PET. For determination of the potential usefulness of MET-PET in living-donor liver transplantation, the present study was strictly limited to the normal pancreas of donors and diseased pancreas of recipients with type 1 diabetes in living-related pancreas transplantation. Eight living donors and 8 recipients with type 1 diabetes who were scheduled for livingrelated pancreas transplantation were enrolled for the evaluation between February 2006 and December 2007 at the ChibaEast National Hospital for biochemical examination and National Institute of Radiological Sciences for PET studies. The mean (SD) age of the subjects without diabetes was 60 (2) years, and that of the patients with type 1 diabetes was 36 (4) years. The mean (SD) duration of diabetes in the patients with type 1 diabetes was 22 (5) years. The mean (SD) body mass index was 23.1 (2.1) kg/m in the subjects without diabetes and 20.0 (1.8) kg/m in patients with type 1 diabetes. The fasting plasma glucose, hemoglobin A1c, and C-peptide levels in the subjects without diabetes and the patients with type 1 diabetes were 88 (2) mg/dL and 104 (49) mg/dL, 5.2% (0.1%) and 6.5% (1.4%), and 1.82 (0) ng/mL and less than 0.05 ng/mL, respectively. All the datawere acquired with a PET/ computed tomography (CT) system (Biograph Duo; Siemens, Munich, Germany). After 6 hours’ fasting, the standard dose of 740 MBq of MET was injected intravenously 30 minutes before imaging. The following settings were used for the CT: 140 kV, 80 mA; gantry rotation time, 0.5 seconds; collimator width, 2 5 mm; section thickness, 5 mm. Positron emission tomography scanning was performed immediately after the CT. The uptake values of MET in the pancreas were measured and expressed as standardized uptake values (SUVs). The SUVs were compared between the subjects without diabetes and the patients with type 1 diabetes and also between the head of the pancreas and body/tail of pancreas in each of the subjects without diabetes and the patients with type 1 diabetes. The statistical significance of the differences was analyzed using the paired t test, and P G 0.05 was considered to denote significance. The representative MET-PET images of the subjects without diabetes and patients with type 1 diabetes are shown. The MET accumulation was higher in the normal pancreata than in the liver (Fig. 1A), whereas it was lower in the diabetic pancreata than in the liver (Fig. 1B). The MET SUVs in the normal pancreata and type 1 diabetic pancreata were 16.1 (0.4) and 8.4 (1.9), respectively. Thus, the normal pancreata showed significantly higher SUVs than the type 1 diabetic pancreata (P G 0.001). The SUVs in all the normal pancreata were more than 14, and those in all the diabetic pancreata were less than 12. The SUVs in the pancreas head and body/tail in the subjects without diabetes were 16.0 (0.4) and 16.0 (1.5), respectively, and the corresponding values in the patients with type 1 diabetes were 8.4 (1.9) and 7.6 (2.1). The SUVs both in the pancreas head and body/tail accumulated equally in the subjects without diabetes and those with type 1 diabetes. Methionine is a precursor of Sadenosylmethionine, which is the universal methyl donor of transmethyl reactions. It is an essential substance for almost all physiological reactions resulting in the formation of methylated products, such as the informational macromolecules of DNA and RNA. Several experimental studies suggest that hypomethylation can influence cellular differentiation and growth. A recent study indicates that advanced diabetes with renal failure may induce changes that predispose to hypomethylation. The hypomethylation metabolic state, which is associated with a low uptake of MET, may be involved in the metabolic disorder associated with severe diabetes, particularly type 1 diabetes. Although the impairment of exocrine functions can occur in both subjects without diabetes and patients with type 1