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© 2018 The Japanese Urological Association Objectives: To evaluate the prognostic value of the warm ischemic time and the validity of the Kidney Donor Profile Index/Kidney Donor Risk Index for predicting the survival of donors after cardiac death grafts. Methods: We retrospectively assessed 315 kidneys retrieved from donors after cardiac death at Fujita Health University Hospital, Toyoake, Aichi, Japan. The Kidney Donor Profile Index/Kidney Donor Risk Index was calculated and the grafts were enrolled. Results: The median follow-up period was 11.9 years. The Kidney Donor Profile Index had a markedly asymmetric distribution (median 94%), and the Kidney Donor Risk Index had high index rates (0.79–2.94, median 1.70). The overall 5-, 10- and 15-year graft survival rates were 67.5%, 52.1% and 38.9%, respectively. The Kidney Donor Profile Index correlated with graft survival. The 5-, 10- and 15-year graft survival rates for the Kidney Donor Profile Index <1.2 were 87.7%, 73.5% and 59.2%; those for the Kidney Donor Risk Index >2.0 were 55.0%, 34.7% and 22.1%, respectively. A Cox multivariate analysis identified the Kidney Donor Risk Index (hazard ratio 2.06, 95% confidence interval 1.48–2.86, P < 0.0001) and warm ischemic time (hazard ratio 1.21, 95% confidence interval 1.09–1.34, P = 0.0010) as independent risk factors for graft loss. The addition of warm ischemic time >30 min had a significant effect, as measured by the C-index (0.708–0.731, P = 0.032), improving the net reclassification improvement score (0.256, P = 0.0039) and integrated discrimination improvement score (0.042, P = 0.0022). Conclusions: The Kidney Donor Profile Index/Kidney Donor Risk Index is a good prognostic tool for determining the outcomes of donors after cardiac death grafts. However, the warm ischemic time should also be included in the allocation system for donors after cardiac death grafts.

© 2018 Japanese Journal of Cancer and Chemotherapy Publishers Inc. All rights reserved. Robotic-assisted surgery has been wide-spreading rapidly as a technique to develop laparoscopic surgery by innovative technological improvement such as high magnifided 3D-image and multi-degree freedom of forceps, leading to safety enhancement and better functional recovery. Robotic surgery in the urological field made it possible to highly fine operation in a narrow field, such as pelvic cavity or retroperitoneal space. Better outcomes were recognized especially in perioperative complications and postoperative QOL recovery than other procedures like open or laparoscopic. According to these results, radical prostatectomy, partial nephrectomy and radical cystectomy were approved for health insurance coverage in 2012, 2016 and 2018, respectively. Robotic-assistance has definitely brought a paradigm shift in urologic surgery. The application to more and more a variety of procedure and the improvement of treatment outcomes are expected in the future.

OBJECTIVES: Contrast-enhanced ultrasonography can evaluate microcirculation. Thus, we used contrast-enhanced ultrasonography in evaluating pancreas graft perfusion and examined the relationship between graft circulation and function.METHODS: Contrast-enhanced ultrasonography was performed in 17 cases within 24 hours and at 1, 3, 5, 7, 14, 21, and 28 days after transplantation (Tx). The time between the time to peak intensity in the parenchyma and that in the vein was defined as delta-Tp(P-V). Graft function was evaluated with oral glucose tolerance test (OGTT) at 1 and 3 months after Tx, and glucagon stimulation test at 1 month after Tx.RESULTS: Differences in delta-Tp(P-V) between individual cases were more significant early after Tx, and delta-Tp(P-V) within 24 hours (delta-Tp[P-V]24h) was used in the subsequent analysis. Delta-Tp(P-V)24 hours showed a negative correlation with C-peptide increment in the glucagon stimulation test and the area under the curve of insulin level in oral glucose tolerance test. The cases were divided into the following 2 groups: the standard group (delta-Tp[P-V]24h ≤6.10 seconds) and the delayed group (>6.10 seconds). The area under the curve of insulin level increased significantly from 1 to 3 months after Tx in the standard group only.CONCLUSIONS: These results suggest that delta-Tp(P-V)24 hours affects insulin secretion after Tx. Contrast-enhanced ultrasonography is useful in predicting endocrine function of the graft.

© 2018 Springer Nature Singapore Pte Ltd. Purpose: In Japan, there have been no national surveys on the incidence of de novo malignancy after solid organ transplantation, which is one of the leading causes of death in transplant recipients. Methods: A questionnaire was distributed to institutions that perform solid organ transplantation in Japan, and clinical information was collected from patients who underwent transplantation between 2001 and 2010 and who exhibited de novo malignancies. Results: Nine thousand two hundred ten solid organ transplants (kidney, 49.9%; liver, 45.9%; heart, 0.9%; lung, 1.2%; pancreas, 1.9%; small intestine, 0.2%) were performed. Four hundred seventy-nine (5.2%) cases of de novo malignancy were identified. The transplanted organs of the patients included the kidney (n = 479, 54.8%), liver (n = 186, 38.8%), heart (n = 5, 0.1%), lung (n = 18, 3.8%), pancreas (n = 9, 1.9%), and small intestine (n = 1, 0.02%). The most common malignancies were post-transplant lymphoproliferative disorder (n = 87) and cancers of the kidney (n = 43), stomach (n = 41), large intestine (n = 41), and lung (n = 36). Conclusions: This is the first national survey of the incidence of de novo malignancy in Japan. Further study is required to identify the risk of de novo malignancy in organ transplant recipients in comparison to the general population, namely the standardized incidence ratio.

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.

After publication of the initial version of the Japanese guidelines for urological surgery in 2007, new surgical techniques have been introduced. Furthermore, several important issues, such as criteria for use of single-dose antimicrobial prophylaxis and control of hospitalized infection, were also established, which led to alterations of the methods used for antimicrobial prophylaxis as well as perioperative management. The purpose of antimicrobial prophylaxis is to protect the surgical wound from contamination by normal bacterial flora. Antimicrobial prophylaxis should be based on penicillins with beta-lactamase inhibitors, or first- or second-generation cephalosporins, though penicillins without beta-lactamase inhibitors should not be prescribed because of the high prevalence of antimicrobial resistance. As an adequate intratissue concentration of the antimicrobial at the surgical site should be accomplished by the time of initiation of surgery, antimicrobial prophylaxis should be started up to 30 min before beginning the operation. Antimicrobial prophylaxis should be terminated within 24 h in clean and clean-contaminated surgery, and within 2 days of surgery using the bowels, because a longer duration is a risk factor for surgical site infection development. Importantly, possible risk factors for surgical site infections include the antimicrobial prophylaxis methodology used as well as others, such as duration of preoperative hospitalization, hand washing, the American Society of Anesthesiologists score, diabetes and smoking history. These guidelines are to be applied only for preoperatively non-infected low-risk patients. In cases with preoperative infection or bacteriuria that can cause a surgical site infection or urinary tract infection after surgery, patients must receive adequate preoperative treatment based on the individual situation.

BackgroundA total of 26 pancreas transplants from brain dead donors, including 21 simultaneous pancreas and kidney (SPK) transplantation procedures, have been performed at Fujita Health University Hospital since the new pancreas transplant program was initiated in August 2012. The objective of this study is to investigate the outcomes of pancreatic transplantation in our facility in first 3 years of the program. MethodsThe background characteristics of the donors and the outcomes of 26 pancreas transplant recipients were analyzed. ResultsThe mean age of the recipients was 44.0years, and all recipients had a long-term history of diabetes (mean: 30.2years). In the SPK cases, the patients also had a long history of hemodialysis (mean: 6.3years). Although the average donor age was 41.0years and more than half of the donors were marginal donors (defined according to Kapur's criteria and Troppmann's criteria), the patient survival and pancreatic graft survival rates were 100% and 91.7%, respectively. Unfortunately, two recipients experienced graft failure due to graft thrombosis, which resulted in graft loss. ConclusionsThe new pancreas transplant program at Fujita Health University has provided excellent outcomes for patients with type 1 diabetes.

Objectives: Kidneys procured from the deceased hold great potential for expanding the donor pool. The aims of the present study were to investigate the post-transplant outcomes of renal allografts recovered from donors after cardiac death, to identify risk factors affecting the renal prognosis and to compare the long-term survival from donors after cardiac death according to the number of risk factors shown by expanded criteria donors. Methods: A total of 443 grafts recovered using an in situ regional cooling technique from 1983 to 2011 were assessed. To assess the combined predictive value of the significant expanded criteria donor risk criteria, the patients were divided into three groups: those with no expanded criteria donor risk factors (no risk), one expanded criteria donor risk factor (single-risk) and two or more expanded criteria donor risk factors (multiple-risk). Results: Among the donor factors, age >= 50 years, hypertension, maximum serum creatinine level >= 1.5 mg/dL and a warm ischemia time >= 30 min were identified as independent predictors of long-term graft failure on multivariate analysis. Regarding the expanded criteria donors criteria for marginal donors, cerebrovascular disease, hypertension and maximum serum creatinine level >= 1.5 mg/dL were identified as significant predictors on univariate analysis. The single-and multiple-risk groups showed 2.01- and 2.40-fold higher risks of graft loss, respectively. Conclusions: Renal grafts recovered from donors after cardiac death donors have a good renal function with an excellent long-term graft survival. However, an increased number of expanded criteria donors risk factors increase the risk of graft loss.

Nephron-sparing surgery has been proven to positively impact the postoperative quality of life for the treatment of small renal tumors, possibly leading to functional improvements. Laparoscopic partial nephrectomy is still one of the most demanding procedures in urological surgery. Laparoscopic partial nephrectomy sometimes results in extended warm ischemic time and severe complications, such as open conversion, postoperative hemorrhage and urine leakage. Robot-assisted partial nephrectomy exploits the advantages offered by the da Vinci Surgical System to laparoscopic partial nephrectomy, equipped with 3-D vision and a better degree in the freedom of surgical instruments. The introduction of the da Vinci Surgical System made nephron-sparing surgery, specifically robot-assisted partial nephrectomy, safe with promising results, leading to the shortening of warm ischemic time and a reduction in perioperative complications. Even for complex and challenging tumors, robotic assistance is expected to provide the benefit of minimally-invasive surgery with safe and satisfactory renal function. Warm ischemic time is the modifiable factor during robot-assisted partial nephrectomy to affect postoperative kidney function. We analyzed the predictive factors for extended warm ischemic time from our robot-assisted partial nephrectomy series. The surface area of the tumor attached to the kidney parenchyma was shown to significantly affect the extended warm ischemic time during robot-assisted partial nephrectomy. In cases with tumor-attached surface area more than 15 cm(2), we should consider switching robot-assisted partial nephrectomy to open partial nephrectomy under cold ischemia if it is imperative. In Japan, a nationwide prospective study has been carried out to show the superiority of robot-assisted partial nephrectomy to laparoscopic partial nephrectomy in improving warm ischemic time and complications. By facilitating robotic technology, robot-assisted partial nephrectomy will be more frequently carried out as a safe, effective and minimally-invasive nephron-sparing surgery procedure.

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.

A 53-year-old woman who had undergone deceased donor kidney transplantation twice, at 35 and 43 years of age, presented with renal impairment. She was infected with hepatitis C virus (HCV). The histology of the graft kidney revealed post-transplant membranous nephropathy (MN) with podocytic infolding and antibody-mediated rejection (AMR). IgG subclass staining showed fine granular deposits of IgG1 and IgG3, but not IgG4, in the glomerular capillary walls. Panel reactive antibody scores for human leukocyte antigen class I and class II were 92.67% and 66.68%, respectively. Thus, this case of post-transplanted MN was considered to be associated with AMR and HCV infection.

A 42-year-old female visited our hospital with the chief complaint of macrohematuria and left lateroabdominal pain. Computed tomography and retrograde pyelogram showed left hydronephroureter and obstructive uropathy which was 20 mm in diameter in the middle ureter. Urine cytology was negative. Ureter biopsy revealed amyloidosis. Our diagnosis was localized amyloidosis of the ureter, because amyloid was not found in other places in her whole body inspection. Partial ureterectomy was performed. Left renal function was preserved. The patient has been free of recurrence for 18 months after 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.

Background. Nutritional status affects clinical outcomes in patients with chronic renal failure. Glucose intolerance, dyslipidemia, obesity, hypertension, and a calcium phosphorus vitamin D imbalance are the major nutritional and metabolic problems that occur in posttransplant patients. In this study, we assessed the daily intake in long-term renal transplant recipients to determine whether they have sufficient nutrients based on the Japanese nutrition recommendations (recommended dietary allowances [RDA] in Japan 2010). Subjects and Methods. Thirty-one renal allograft recipients followed for >10 years (median, 16.3) were recruited. The median serum creatinine level was 1.2 g/dL (95% CI, 0.6-3.4). We estimated the intake of nutrients, including protein and salt, using a simple food frequency questionnaire. Results. The median body mass index was 20.1 kg/m(2). The median total energy intake was 1566 kcal/d (95% CI, 892-2556). The daily intake of protein and salt was 65.1 and 9.1 g/d, respectively. The calcium, iron, vitamin D, and vitamin K intakes were 423 mg, 7.0 mg/d, 9.7 mu g/d, and 197 mu g/d, respectively. Patients with dyslipidemia displayed greater amounts of lipid and calcium than those with normal lipid levels. Discussion. Our findings suggest that long-term renal transplant recipients in Japan seem to restrict caloric intake, while maintaining appropriate intake of protein, lipids, carbohydrates, and vitamins A, D, and K. However, daily calcium and iron intake were insufficient; salt intake was greater than the recommended dietary allowances in all subjects. In patients with dyslipidemia, calcium intake was lower than those in patients without dyslipidemia, although their intake of lipids was also lower than those without dyslipidemia. Conclusion. Nutritional guidance beginning during the early posttransplant phase helps to foster a healthy body mass index and nutritional balances for long-term renal transplant recipients. However, greater salt restriction was needed, and additional nutritional guidance aiming to prevent osteoporosis seems to be considered.

The concept of brain death was introduced with the Harvard criteria in 1968 [1]. However, brain dead (DBD) donors were not used for organ transplantation in Japan until the enforcement of the Japanese Organ Transplant Law in 1997. Therefore, prior to this, all cadaveric kidney transplantations were performed using DBD donors according to the law regarding DCD for cornea and kidney transplantation. Due to a severe shortage of deceased donors, kidney transplantation is mainly performed using living donors in Japan. Changes in the number of kidney transplantation (Fig. 14.1) showed 212 patients underwent kidney transplantation from deceased donor in 2011, while 1,389 patients underwent living donor kidney transplantation [2]. Even after the enforcement of the Japanese Organ Transplant Law in 1997, the number of DBD donors remained low, such were only several donors per year. Although the number of DBD donors has been increased since the enforcement of the revised Japanese Organ Transplant Law in July 2010, deceased donor kidney transplantation is still mainly performed from DCD donors. Therefore, a history of deceased donor kidney transplantation is almost equal to the history of kidney transplantation using DCD donors. In March 1995, Koostra et al. have introduced the classification of DCD donors into four categories (Table 14.1) [3]. Category III, in which donors were on awaiting cardiac arrest after withdrawal of life-sustaining therapy, is considered to be suitable for organ donation for transplantation because of a short period of warm ischemia. The condition of DCD donors in Japan is, however, different from those in other countries like the United States and Europe. The withdrawal of life-sustaining therapy (respirator) is rarely performed even though the donor is diagnosed to be a brain death except for an approval of donor families for the donation as DBD donors. Therefore, the DCD donors in Japan are difficult to be classified to any Maastricht categories. The condition of procurement is uncontrolled because of no withdrawal of respirator and long-lasting hypotension and oliguria (anuria) are frequently observed until cardiac arrest. In Japan, early kidney transplantation from DCD donors was performed by regional sharing rules. Several transplantation centers in each region, in which the devoted transplant surgeons were working, conducted the registration of the recipients, procurement, organ sharing, and transplantation. Since Japan Organ Transplant Network (JOTNW) was established in 1995, the regulation of registration of the patients, procurement, organ sharing, and transplantation in all organs including the heart, lung, liver, pancreas, small intestine, and kidney have been conducted by JOTNW. In this chapter, we describe the current status of kidney transplantation using DCD donors in Japan.

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.

Kidneys procured by donation after cardiac death (DCD) may increase the donor pool but are associated with high incidence of delayed graft function (DGF). Urinary liver-type fatty acid-binding protein (L-FABP) level is an early biomarker of renal injury after kidney transplantation (KTx); however, its utility is limited in DGF cases owing to urine sample unavailability. We examined whether serum L-FABP level predicts functional recovery of transplanted DCD kidneys. Consecutive patients undergoing KTx from living related donors (LD), brain-dead donors (BD), or DCD were retrospectively enrolled. Serum L-FABP levels were measured from samples collected before and after KTx. Serum L-FABP decreased rapidly in patients with immediate function, slowly in DGF patients, and somewhat increased in DGF patients requiring hemodialysis (HD) for >1wk. Receiver-operating characteristic curve analysis demonstrated that DGF was predicted with 84% sensitivity (SE) and 86% specificity (SP) at cutoff of 9.0ng/mL on post-operative day (POD) 1 and 68% SE and 90% SP at 6.0 on POD 2. DGF >7d was predicted with 83% SE and 78% SP at 11.0 on POD 1 and 67% SE and 78% SP at 6.5 on POD 2. Serum L-FABP levels may predict graft recovery and need for HD after DCD KTx.

Background. Currently, there are no published data on pharmacokinetics (PK) of everolimus in combination with cyclosporine in Japanese renal transplant patients. We evaluated the PK of everolimus in Japanese de novo renal transplant patients who received everolimus in combination with cyclosporine. Methods. In this phase 3, multicenter, randomized, open-label study, patients were randomized (1:1) to 1 of the 2 groups: everolimus 1.5 mg (targeted C-0 of 3-8 ng/mL) plus reduced-dose cyclosporine or mycophenolate mofetil 2 g/d plus standard-dose cyclosporine. PK assessments for everolimus were performed on day 28 (month 1) in the PK subpopulation. Results. A total of 11 patients (7 men), mean age 47.5 +/- 11.21 years, were enrolled for PK analysis of everolimus. Starting at 1.5 mg (0.75 mg twice a day), the mean dose over a period of 28 days was 0.705 +/- 0.1011 mg. Everolimus mean trough concentration was 4.307 +/- 1.2459 ng/mL and mean peak concentration was 13.539 +/- 3.5330 ng/mL, which peaked at 1 to 2 hours postdose. The average concentration was 7.558 +/- 1.4723 ng/mL, area under the concentration-time curve was 90.70 +/- 17.667 ng h/mL, and peak-trough fluctuation was 122.6%. The PK parameters of everolimus were comparable to those in the earlier phase 3 studies (A2306 and A2307). The mean everolimus trough levels were within the target ranges at all time points ranging from 3.4 to 5.5 ng/mL (everolimus 0.75 mg twice a day, safety population). The majority of patients (>85% from day 7 onward) were maintained within the targeted everolimus trough blood levels (safety population). These data were similar to a non-Japanese study (A2309). Conclusions. The pharmacokinetic characteristics of everolimus in Japanese de novo renal transplant patients did not differ from those previously observed in non-Japanese patients, hence the same dosage of everolimus may be acceptable in Japanese patients.

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 beta-cell function after pancreas transplantation is necessary. Methods. Pancreatic beta-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 Delta CPR 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 Delta CPR 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 Delta CPR after glucagon injection could reflect beta-cell function for post-pancreas transplant patients, and glucagon stimulation test could give us additional information to predict insulin-free treatment.

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.

Purpose: Kidneys procured from donors after cardiac death hold great potential to expand the donor pool. However, they have not yet been fully used, in part due to the high incidence of delayed graft function. Although urine neutrophil gelatinase-associated lipocalin is a well-known early biomarker for renal injury after kidney transplantation, its usefulness is limited in cases with delayed graft function because of the unavailability of a urine sample. We evaluated serum neutrophil gelatinase-associated lipocalin as a potential biomarker to predict the functional recovery of kidneys transplanted from donors after cardiac death. Materials and Methods: Consecutive patients transplanted with a kidney from a living related (39), brain dead (1) or post-cardiac death (27) donor were retrospectively enrolled in the study. Serum samples were collected serially before and after kidney transplantation. Serum neutrophil gelatinase-associated lipocalin was measured using the ARCHITECT (R) assay. Results: Average serum neutrophil gelatinase-associated lipocalin was markedly high during the pre transplantation period. It decreased rapidly after transplantation. The slope of the decrease correlated well with the recovery period. By analyzing ROC curves we determined cutoffs to predict immediate, slow or delayed graft function requiring hemodialysis for longer than 1 week with high sensitivity and specificity. Conclusions: These data suggest that serial monitoring of serum neutrophil gelatinase-associated lipocalin may allow us to predict graft recovery and the need for hemodialysis after kidney transplantation from a donor after cardiac death.

In the urological operative field, antimicrobial prophylaxis seems to be important when performing a transurethral resection in order to prevent perioperative febrile urinary tract infection and urosepsis. In order to draw up the original Japanese guidelines for antimicrobial prophylaxis, the Japanese Urological Association(JUA) established the working group and accomplished the drawing up of the new guidelines, which were published in the Journal of Japanese Urology in 2006. Then 5 years later, in order to examine the validity of our Japanese guidelines, we sent out questionnaires to urological surgeons which asked about the rates of agreement between the antibiotics they were administering and the guidelines-recommended antibiotics, and also regarding the incidence of perioperative infections. For transurethral resection of the prostate(TUR-P), the questionnaires were sent out to 100 members of the JUA and there were 75 respondents (response rate of 75%). The rate of agreement with the Japanese guideline was 79.6%, and the rate of perioperative infections in 92.3% of the respondents' institutes was less than 5%. For transurethral resection of bladder tumors(TUR-Bt), the questionnaires were sent out to 114 members of the JUA and there were 89 respondents (response rate of 78.1%). The rate of agreement with the Japanese guideline was 77.6%, and the rate of perioperative infections in 95.4% of the respondents' institutes was less than 5%. The results of the same questionnaire survey, which were examined in 1995, demonstrated that we could not prevent the occurrence of about 5% perioperative infections against more than 7 days' antimicrobial prophylaxis. In accordance with previous data, we can accept appropriate antimicrobial prophylaxis, if the prophylaxis suppresses the occurrence of perioperative infections to less than 5%. This study has shown that the antimicrobial prophylaxis for transurethral resection suggested by the Japanese guidelines was appropriate.

Holmium laser enucleation of the prostate (HoLEP) has been established as a procedure for the treatment of patients with benign prostate hyperplasia, instead of transurethral resection of prostate (TURP). To determine the appropriate antimicrobial prophylaxis for the prevention of perioperative urinary tract infection following HoLEP we sent a questionnaire to 79 institutes belonging to the Japanese Urological Association. We surveyed 1) the performance of HoLEP, 2) number of HoLEP performed in 2009, 3) antimicrobial agents and the term of the administration for prophylaxis, 4) rate of perioperative infections, and 5) usage of other antimicrobial prophylaxis in HoLEP, as compared with in TUR-P. We received answers from 59 institutes (74.9%). We examined 43 responses, which were obtained from executive members who performed more than eleven cases of HoLEP in 2009. Thirty-one of these institutes (72.1%) indicated parenteral antibiotics three of them adopted oral antibiotics, and nine of them added oral antibiotics following parenteral antibiotics. In 40 of them (93.0%), the rate of perioperative infections was reported to be fewer than 5%. Twenty-seven of them (62. 7%) adopted the same schedule for the prophylaxis in both HoLEP and TUR-P. Eleven of them indicated shorter antimicrobial usage in HoLEP than in TUR-P. Ten of the eleven institutes reported that the rate of perioperative infections in HoLEP had been lower than in TUR-P. Our questionnaire survey demonstrated that shorter antimicrobial prophylaxis might be possible in HoLEP than in TUR-P.

【緒言】2006年の日本泌尿器科雑誌に「泌尿器科領域における周術期感染予防ガイドライン」が掲載されて2年以上が経過する。今回、われわれはガイドラインを検証する目的で周術期予防投与に関するアンケート調査を実施した。【対象・方法】本学会の評議委員が在籍する全国59施設にアンケート用紙を送付した。内容は(1)ガイドラインが認知されているか、(2)ガイドラインに沿った投与方法がおこなわれているか、(3)ガイドライン以外の投与方法はどのような内容か、(4)それぞれの術後感染症の発生頻度について意見を求めた。【結果】回答率は62.7%で、質問(1)は22/31=71.0%であった。質問(2)は尿路を開放しない手術で24/29=82.8%、内視鏡手術で16/21=76.2%、内視鏡検査で26/26=100%、尿路を開放する手術で18/28=64.3%、体腔鏡手術で16/20=80%であった。質問(3)は経口抗菌薬を追加投与する施設が目立ち、質問(4)は5%以下が9割以上を占めていた。【考察】ガイドラインの認知度については予想より高かった。さらに抗菌薬の使用方法はガイドラインに沿った、もしくは類似した内容であり、術後の感染発生頻度も低く抑えられていた。今後の課題としては、経口剤追加投与の必要性などをさらに検討して、ガイドラインとしての完成度を高めることが必要になるであろう。(著者抄録)

(Objectives): For the management of patients with small renal tumor, laparoscopic partial nephrectomy (LPN) provides similar oncological control as radical nephrectomy (RN) and is superior to RN with respect to preserving renal function and preventing chronic kidney disease (CKD). The challenge of LPN is to resect a tumor in a bloodless field within a limited warm ischemia time (WIT), followed by hemostatic Tenorrhaphy under restricted movement of laparoscopic forceps. Therefore, LPN still remains challenging to even experienced laparoscopic surgeon. DaVinci device improved the movability of forceps in LPN and provided three-dimensional visualization. We evaluated outcome and safety of our first series of robot-assisted laparoscopic partial nephrectomy (RALPN) for localized kidney tumor. There was no previous report of RALPN undertaken in our country. (Patients and methods): Since August 2010, our team carried out RALPN for a total of five cases of renal tumor. There were four males and one female with an age range of 41 to 65 years-old. Size of tumor ranged from 15 to 28 mm, located in exophytic region, and four cases in right side and one in left. RALPN was undertaken by single surgeon through transperitoneal approach in two cases and retroperitoneal in tree. (Results): RALPN was completed in all patients without conversion to open or hand-assisted surgery. The median operative time and the estimated blood loss were 189 minutes, ranged from 150 to 264, and 29 ml, from 10 to 50, respectively. The median volume of removed tumor and the length of WIT were 7 g, ranged from 4 to 13 g, and 18 minutes, from 13 to 26 minutes, respectively. No complications or reoperations were associated during or post our RALPN cases. Pathological examination of removed tumor showed renal cell carcinoma with negative surgical margin in all cases. (Conclusions): Introduction of daVinci™ device to LPN made this procedure, RALPN, a secured and promising one, which leading to shorten the WIT and to achieve satisfied Tenorrhaphy. Even for the complex and technically challenging renal tumors, robotic assistance is expected to provide patients the benefit of minimally invasive surgery with safety and satisfactory renal function. © 2011 Japanese Urological Association.

Purpose: Renal scarring is a serious complication that often occurs with chronic pyelonephritis in the presence of vesicoureteral reflux. In a previous study we established a rat model of renal scarring in which we found the up-regulation of neutrophil-gelatinase associated lipocalin at the mRNA and protein levels. In this study we evaluated urinary neutrophil-gelatinase associated lipocalin as a potential biomarker for progression of renal scarring in patients with vesicoureteral reflux. Materials and Methods: A total of 34 patients diagnosed with vesicoureteral reflux without evidence of current urinary tract infection and 28 normal healthy children were enrolled in this study. Renal scars were evaluated by (99m)technetium dimercapto-succinic acid renal scan in 24 of the reflux cases. Urinary neutrophil-gelatinase associated lipocalin levels were monitored by ELISA. Results: In normal subjects urinary neutrophil-gelatinase associated lipocalin was high during infancy, decreased rapidly within the following year and reached a low stable level from age 3 years onward. Urinary neutrophil-gelatinase associated lipocalin levels, normalized to age matched standards, were significantly increased in patients with vesicoureteral reflux compared to controls. These levels did not correlate with reflux grade, but were significantly higher in patients with radiological evidence of renal scarring irrespective of reflux grade. Conclusions: Estimation of urinary neutrophil-gelatinase associated lipocalin may be useful as a noninvasive diagnostic or prognostic biomarker for renal scarring.

Donors after cardiac death (DCD) have recently become an important source of renal transplants to alleviate the shortage of renal grafts in kidney transplantation (KTx), although DCD kidneys often have complications associated with a delayed graft function (DGF). A microarray-based approach using renal biopsy samples obtained at 1 h after KTx from DCD identified the tissue inhibitor of metalloproteinases 1 (TIMP-1) gene as a potential predictive marker for DGF. The current study measured serum TIMP-1 in patients undergoing KTx and analyzed the time course after KTx. The average serum TIMP-1 level before KTx was 240 +/- 10 ng/ml (n = 34). In patients undergoing KTx from a living donor (n = 23), the serum TIMP-1 levels showed no increase after KTx (POD1: 226 +/- 12, POD2: 211 +/- 12, and POD3: 195 +/- 10 ng/ml), but in one case, the only patient who required post-KTx HD due to DGF, the level on POD1 was the highest among subjects (361 ng/ml). In contrast, patients undergoing KTx from DCDs (n = 11), the serum TIMP-1 levels increased rapidly after a KTx (POD1 : 418 +/-+/- 32, POD2: 385 +/- 42, and POD3: 278 +/- 25 ng/ml). However, two patients who avoided post-KTx HD due to the immediate function of the graft did not show increased levels (<370 ng/ml) on either POD1 or POD2. The peak serum TIMP-1 values appeared to correlate to the post-KTx dialysis period. Furthermore, the increment of serum TIMP-1 on the early POD was found to be predictive of immediate or delayed function of the grafts. These data suggest that monitoring of serum TIMP-1 levels allow the prediction of graft recovery and the need for HD after a KTx from a DCD.

Purpose: Recurrent upper urinary tract infection is a common complication of vesicoureteral. reflux that often leads to irreversible renal scarring. In our previous study of a rat model of renal bacterial infection we performed global gene expression profiling of the kidney during the onset of renal scarring. We have further investigated the product of an up-regulated gene product, NGAL, in this animal model to evaluate its potential usefulness as a biomarker of renal scarring. Materials and Methods: Renal NGAL mRNA and protein levels were examined by real-time polymerase chain reaction, Western blot and immunohistochemistry. Urinary NGAL levels were monitored by direct enzyme-linked immunosorbent assay. Results: Rat renal NGAL mRNA and protein levels were found to be increased soon after bacterial injection. They then decreased rapidly but subsequently persisted at high levels until the 6-week time point after injection. On histological analysis we found that NGAL protein was overproduced in macrophages and renal tubular cells 2 weeks after injection. However, renal tubular cells continued to produce NGAL 6 weeks after injection, whereas this expression was lost in infiltrating cells. Rat urinary NGAL levels were also markedly increased at the early stages of infection and they persisted at high levels throughout the latter stages of the experiment. Conclusions: Urinary NGAL may be a potential noninvasive diagnostic biomarker of renal scarring.

Because of the worldwide shortage of renal grafts, kidney transplantation (KTx) from donors after cardiac death (DCD) is an alternative way to obtain KTx from brain-dead donors. Although the prognosis of DCD KTx is gradually improving, the graft often undergoes delayed graft function (DGF), rendering the control of DGF essential for post-KTx patient care. In an attempt to characterize etiology of DGF, genome-wide gene expression profiling was performed using renal biopsy samples performed at I h after KTx from DCD and the data were compared with those of KTx from living donors (LD). A total of 526 genes were differentially expressed between them. Genes involved in acute inflammation were activated, while metabolic pathways were consistently downregulated in DCD. These findings imply the inferior performance of the DCD grafts relative to LD grafts. Several genes were identified where the expression levels were correlated well with parameters indicating short- and long-term prognosis of the DCD patients. In addition, several genes encoding secretory proteins were identified that might reflect the performance of the graft and be potential noninvasive biomarkers. These data provide a good source for candidates of biomarkers that are potentially useful for the control of DGF.

Renal scarring is a serious complication of chronic pyelonephritis that occurs due to vesicoureteral reflux. In our study, we performed global expression profiling of the kidney during renal scarring formation in a rat pyelonephritis model. An inoculum of Escherichia coli was injected directly into the renal cortex. Histologically, renal scarring developed during the 3-to-4 week period after injection. The time-course expression profile of 18,442 genes was then analyzed using microarrays, followed by validation with real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Most of the genes found to be up-regulated during renal scarring are associated with immune and defense responses, including cytokines, chemokines and their receptors, complement factors, adhesion molecules and extracellular matrix proteins. These genes were up-regulated as early as 1 week after injection, when no fibrotic changes were yet evident, peaked at 2 weeks, and gradually decreased thereafter. However, a subset of cytokine genes was found to be persistently activated even at 6 weeks after injection, including interleukin (IL)-1 beta, transforming growth factor (TGF)-beta, and IL-3. Further statistical analysis indicated that the pathways mediated by these cytokines are activated concomitantly with renal scarring formation. The products of these genes may thus potentially be novel non-invasive diagnostic or prognostic biomarkers of renal scarring.

We examined the effectiveness of supplemental administration of flavoxate hydrochloride in patients with benign prostatic hyperplasia (BPH) whose nocturia was not adequately relieved by an α1-adrenoceptor blocker. Fifty-two patients who had two or more nocturnal micturition after administration of tamsulosin hydrochloride or naftopidil for 4 weeks or more received 400-600 mg of flavoxate hydrochloride in addition to an α1-adrenoceptor blocker for another 8-12 weeks. With supplemental administration of flavoxate hydrochloride, significant improvement was observed in the number of nocturnal micturition, total International Prostate Sympton Score, quality of life score and BPH impact index. No significant change was observed in the voided volume, Qmax, voiding time and residual urine volume. Supplemental administration of flavoxate hydrochloride is therefore effective for the improvement of nocturia and QOL in BPH patients resistant to an α1-adrenoceptor blocker.

Zoledronic acid is reported to significantly reduce skeletal morbidity and prolong time to bone lesion progression in patients with bone metastases from various malignant tumors including renal cell carcinoma. Due to renal uptake and elimination of zoledronic acid, however, it is difficult to control dose alignment in patients with kidney dysfunction. We reviewed significance of hemodialysis and monitoring of serum creatinine and calcium in patients with ESRD. (Cases) We experienced two cases of end-stage renal disease (ESRD) with bone metastases from advanced renal cell carcinoma. Zoledronic acid was given to both patients by 15 minutes intravenous infusion followed by hemodialysis 24 hours later. Systemic cytokine infusion and oral thalidomide were also given to both patients. Level of serum calcium reduced in one case two weeks later, and treated by calcium administration. No other adverse effects were noted for more than six months of combination therapy. Both cases maintained stable disease not only for bone metastases but also for the systemic condition without any organ failure. Even in patients under maintenance hemodialysis, zoledronic acid can be given with certain safety and efficacy by hemodialysis 24 hours after administration and intense monitoring of serum calcium level. We think this is the first report of zoledronic acid treatment to ESRD patients with bone metastases from malignant tumors.

Because of a worldwide shortage of renal grafts, kidneys procured from donors after cardiac death (DCD) have recently become an important source of renal transplants. However, DCD kidneys often have complications with delayed graft function (DGF) and recipients require hemodialysis (HD) in the early period after kidney transplantation (KTx). This study evaluated serum NGAL as a potential specific parameter to predict early functional recovery of transplanted DCD kidneys. The average serum neutrophil gelatinase-associated lipocalin (NGAL) level in normal samples was 53 +/- 30 ng/ml, while that in patients with chronic renal failure requiring HD was markedly raised at 963 33 ng/ml. In patients undergoing a living-related KTx from a living donor (n = 11), serum NGAL level decreased rapidly after KTx, and only in two cases, with serum NGAL levels over 400 ng/ml on postoperative day 1 (POD1), was HD required due to DGF. In contrast, all patients undergoing a KTx from a DCD (n = 5) required HD due to DGF. Even in these cases, serum NGAL levels decreased rapidly several days after a KTx prior to the recovery of urine output and preceding the decrease in serum creatinine level. The pattern of decline in serum NGAL was biphasic, the decrease after the second peak indicating a functional recovery within the next several days. These data suggest that monitoring of serum NGAL levels may allow us to predict graft recovery and the need for HD after a KTx from a DCD.

Stress urinary incontinence (SUI) is a major urologie health problem and the number of patients with SUI will rise dramatically as the population of elderly people continues to increase in Japan. This condition causes unnecessary and detrimental psychological distress, social isolation, and public expense for care. Surgery remains the cornerstone of treatment for female SUI and also in those who have failed to improve with conservative measures. Many surgical procedures, however, have been described with varying degree of success. The ideal surgical treatment for this disease should be effective in QOL improvement, minimal invasive and durable for the long-term. Based on a new understanding of the pathophysiology of SUI as well as the development of surgical techniques and devices, mid urethral sling operations such as TVT (tension-free vaginal tape) have become widely used and they provide significant short-term and long-term cure rates. However, perioperative complications, including serious problems like bowel, vascular and bladder injuries have been reported. Most complications are related to blind trocar passage in the retropubic space. The alternative procedure transobturator procedure was developed to minimize these complications, in which tape is introduced through the obturator foramen. This technique provides high short-term cure rates, similar to those achieved with TVT, but with fewer complications. A number of injectables have been used for the treatment of SUI, including collagen, coated-beeds and Teflon. Although injectable treatment is convenient and minimally invasive, efficacy and durability are lower than other surgical procedures. Modification by tissue-engineering techniques using autologous stem cells or precursors of mature cells showed regeneration and reconstitution of urinary sphincteric function. In the future this strategy may be an attractive therapy for SUI. The choice of operation should be tailored to suit each individual case based on the clinical and urodynamic findings, as well as the age and the expectations of treatment outcome.

The objective is to investigate the outcome of transplantation using kidney grafts from donors after cardiac death (DCDs) with a total ischemia time (TIT) longer than 24 h. All 373 kidneys were procured from DCDs. They were procured using the in-situ regional cooling technique. Grafts were classified into two groups according to TIT. Fifty-three grafts had a TIT longer than 24 h (group 1), and the other 320 grafts (group 2) were less than 24 h. The numbers of never functioning grafts (PGF) were 3 in group 1 (5.7%) and 17 in group 2 (5.3%), a nonsignificant difference. Graft survival rates at 3, 5 and 10 years posttransplant were 84.9%, 73.0% and 64.1% in group 1, and 76.3%, 69.9% and 57.1% in group 2, which demonstrate no significant difference. The significant risk factors for graft failure were donor age, serum creatinine level on hospitalization and WIT. However, TIT longer than 24 h was not employed. Multivariate logistic regression indicated that only WIT was associated with an increase in the risk of PGF. Our results demonstrate that kidneys from DCDs, even if their TIT is more than 24 h, should be considered a worthwhile source of renal grafts.