Kazunori Otsuki

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 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

Preoperative evaluation of residual liver function for extended hepatic resection with positron emission tomography and l-[methyl-11C] methionine

To evaluate residual liver functional reserve before major hepatectomy, volumetry of the residual liver was measured by computed tomography (CT) and the uptake of l-[methyl-11C] methionine of the residual liver was expressed by differential absorption ratio (DAR) with positron emission tomography (PET). Residual liver functional volume was quantified as the functional volume index (FVI). FVI of 11 normal whole liver was 8697 ± 2009 (mean S.D.). Cases, 11, of malignant liver tumors with obstructive jaundice underwent major hepatectomy. FVI of the eight patients (5561 ± 1087) who had good course after operation was significantly higher than that of the other cases (266 +- 685) died of liver failure (P < 0.005). FVI is a useful index to quantify residual liver functional reserve to avoid liver failure after major hepatectomy.

Focal segmental glomerular sclerosis recurrence with massive proteinuria and anuria immediately after kidney transplantation

Here, we report a case of focal segmental glomerular sclerosis (FSGS) recurrence immediately (47 minutes) after transplantation. A 1‐hour biopsy specimen showed large periodic acid‐Schiff–positive granules within the cells of the swollen proximal tubule, while electron microscopy revealed podocyte swelling and partial foot process effacement. These findings were worse on day 2 biopsy. Massive proteinuria and anuria were then observed. Two courses (2 × 2 times) of plasmapheresis and rituximab were administered, and the graft function gradually recovered. A day 22 biopsy specimen showed improvement in findings compared to those observed on day 2. One year after transplantation, no signs of FSGS recurrence are evident, and graft function remains good.

A Review of Autologous Islet Transplantation.

Autologous islet transplantation after total or semitotal pancreatectomy aims to preserve insulin secretory function and prevent the onset of diabetes. The major indication for pancreatectomy is chronic pancreatitis with severe abdominal pain, a benign pancreatic tumor, and trauma. The metabolic outcome of autologous islet transplantation is better than that of allogeneic transplantation and depends on the number of transplanted islets. Achieving islet isolation from a fibrous or damaged pancreas is one of the biggest challenges of autologous islet transplantation; a major complication is portal vein thrombosis after crude islet infusion. However, the incidence of portal vein thrombosis has decreased as islet preparation techniques have improved over time.

Results of Islet Isolation and Their Relationship to the Clinical Outcome of Kidney Transplantation in Cases Where Both Grafts Are Harvested From the Same Non-Heart-Beating Donor

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.

Assessment of residual liver functional reserve after portal embolization with positron emission tomography usingl-[methyl-11C] methionine and computed tomography

Hepatic functional reserve after portal embolization was assessed in eight patients according to the functional volume index (FVI), a new index obtained using positron emission tomography (PET) withl-[methyl-11C] methionine. FVI in residual liver was 1744–5252 (mean, 3441) (normal range, 3106–6211) before percutaneous transhepatic portal embolization (PTPE) and 2457–6906 (mean, 4590) after PTPE. FVI exceeded 4000 in five patients and did not reach 4000 in three patients after PTPE. Two patients with FVI values of more than 4000 survived after hepatectomy and one with FVI under 4000 died of liver failure. FVI is a useful criterion for determining indications for PTPE; a value exceeding 4000 is needed before major hepatectomy can be safely performed after PTPE.

Summary of Retroperitoneoscopic Nephrectomy for Living Donor Kidney Transplantation in a Single Institution.

Introduction It is most important team for living donations to make safer and to reduce operating stress. Endoscopic surgery is thought to be a useful operating procedure for solving these problems. For living donor nephrectomy, we have performed retroperitoneoscopic approach (RDN), because of its less intra-abdominal complications such as bleeding and intestinal injury than trans-abdominal approach. However, the frank incision used for retrieving a kidney graft had thought to be more invasive with damages for abdominal muscles by cutting. So, we have used a single-site retroperitoneoscopic living donor nephrectomy (SSRDN) with GelPOINT® (Applied Medical, USA) We report the summary and advantage of SSRDN in our institution in this presentation. Materials and Procedures Three hundred and fifty-eight living donors were performed RDN for kidney transplantation at Chiba-East National Hospital between April 2004 and July 2017. Recently, with 30 cases, we performed SSRDN. With this procedure, donors were positioned in the lateral position, and a 7-cm-long flank incision was made in the lateral abdomen. The incision was extended to the retroperitoneal space using the muscle-splitting technique. After expanding the retroperitoneal space, a GelPOINT was placed in the incision. Three ports were placed on the GelPOINT, and subsequent procedure was the same as those used in conventional RDN. In the last of this procedure, kidney graft was directly retrieved through the GelPOINT incision. Results Except one case converted for bleeding, 29 cases of SSRDN were performed successfully without any complications and all 30 donors were discharged hospital at estimated day. The mean age and body mass index of the SSRDN donors were 59.6±8.0 years old (55.3±10.8 years old with conventional RDN) and 22.4±2.6 kg/m2 (23.2±3.0 kg/m2), respectively. The mean operative time was 221±53 minutes (227±55 minutes), warm ischemic time was 4.0±1.2 minutes (4.0±1.6 minutes), blood loss was 53±72 mL (58±71 mL) and mean hospital stay after operation was 5.9±0.8 (6.3±1.4 days). No statistical differences were found between SSRDN and conventional RDN. Postoperative graft function (serum creatinine level) was good as conventional RDN and delayed graft function was not observed in any of the SSRDN recipients. Conclusion SSRDN would be useful technique for living donor operation of kidney transplantation. We have carried out this operation more safely and less invasively than conventional RDN. In this presentation, we demonstrate that SSRDN would have advantages of safeness, minimal invasion, and short hospital stay in living donor kidney transplantation.

Effectivity of Hypothermic Machine Perfusion Preservation for Non-Heart-Beating Donor Kidney Transplantation in Japan

Background In Japan, brain-dead donors have been increased by revised Act of Organ Transplantation, however, insufficiency of deceased donors is still serious problem. In kidney transplantation, it is important to use marginal donors such as non-heart-beating donors for solving this problem. Static cold storage (SCS) is the most widely used organ preservation method for deceased donor, and in Japan it is now the only technique for kidney preservation, however, hypothermic machine perfusion preservation (HMP) technique may improve better outcomes than SCS. HMP technology has had a major impact in circumventing ischemic injury in kidney transplantation in western countries. In this presentation, we report efficiency of HMP method for preservation of long ischemic kidney grafts in beagle and case reports of clinical usage to kidney transplantation of non-heat-beating donor in Japan. Methods Young beagles were used as autonomic HMP transplantation model. After general anesthesia of beagles, left renal artery and vein were made ligation, after 30 min warm ischemia time (WIT) in situ, the left kidney was harvested. Each harvested kidney was assigned to one of two preservation treatment groups; SCS group (storage in UW solution at 2-4°C for 24h, n=5); HMP group (storage on LifePort® (Organ Recovery Systems), at 4-6°C on 30 mmHg pressure for 24h with KPS-1 solution, n=5). After the storage, wedge biopsies were taken for histological evaluation. The preserved graft was transplanted to the same beagle in left iliac fossa and removed right kidney. After the operation, recipient survival and graft qualities (urine output, serum creatinine, sodium and potassium) were checked as the clinical outcomes. Results All recipients of HMP group survived, however, three recipients of SCS group were dead with uremia. Serum creatinine level of HMP group was under 4mg/dL in all post-operation period and reduced under 1.5mg/dL after 11days of post-operation. The other hands, those of SCS group went up over 5mg/dL and did not reduce under 3mg/dL. In histological findings, HE staining revealed that a little bit interstitial edema was exist with HMP groups, and remarkable interstitial edema and vaculolation were exist with SCS group. Clinical Cases We performed three cases of renal transplant with HMP graft from non-heart-beating donor. The all three recipients were discharged hospital without any complications with achieved withdrawal of hemodialysis. HMP reduced the duration of delayed graft function and graft function with HMP was same as that with SCS. Conclusion In this experiment, we indicate that HMP would be better for long term WIT kidney model compared with SCS method in beagles. We experienced three clinical cases of non-heart-beating donor kidney transplantation with LifePort® preserved graft in Japan. It suggests that with marginal donor that is non-heart-beating and is with long agony, HMP should be paid more tribute to than SCS technique.

Renal Autotransplantation and Extracorporeal Nephron-Sparing Surgery for De Novo Renal Cell Carcinoma in a Kidney Allograft

Abstract De novo renal cell carcinoma (RCC) rarely occurs in kidney allografts; however, the risk of RCC in these patients is 100-fold that of the general healthy population. Although total nephrectomy has been the standard treatment for kidney allograft RCC, several authors have reported that early-stage RCC in kidney allografts was successfully treated with nephron-sparing surgery. We herein describe a new procedure involving renal autotransplantation and extracorporeal nephron-sparing surgery, which was performed to treat de novo RCC near the hilum of a transplanted kidney. In the 22 months since transplantation, the patients renal function has been favorable, and no recurrence has been observed. In conclusion, renal autotransplantation is a feasible technique for the treatment of RCC in kidney allografts, especially RCC located near the hilum.