Y. Sawada

Sulfoquinovosylacylpropanediol is a novel potent radiosensitizer in prostate cancer.

To examine the effects of combined treatment with sulfoquinovosylacylpropanediol and X‐ray irradiation on the remodeling of the prostate cancer microenvironment, including angiogenic and hypoxic characteristics.

Retroperitoneoscopic donor nephrectomy with multiple renal arteries does not affect graft survival and ureteral complications.

Background Outcomes of retroperitoneoscopic procurement of living kidneys with multiple renal arteries (MRA) in the recipients are largely unknown. Our aim is to access the effect of kidney allografts with MRA on donor and recipient outcomes after pure retroperitoneoscopic live donor nephrectomy (RPLDN). Methods From July 2001 to August 2010, 533 patients underwent live donor kidney transplants with allografts procured by RPLDN at our center. Of these 533 transplants, 406, 105, and 22 patients had one, two, and three renal arteries, respectively. We compared the retrospectively collected clinical data of each donor with MRA and the recipient using those with single renal artery as controls. Results Significant differences were found among the one–renal artery and three–renal artery groups regarding operative time, estimated blood loss, warm and cold ischemic time, and incidence of slow graft function (SGF). However, there was no significant difference regarding patient and graft survival among the three groups. Major complications, such as open conversion, bleeding, and blood transfusion, were not found in patients with MRA. Five ureteral complications occurred. Of these, there was one patient with MRA. In univariate analysis, MRA patients had a risk factor of developing SGF (P=0.005) but not ureteral complications following RPLDN. Conclusion Kidneys with MRA after RPLDN increase the risk of SGF in recipients. However, they provide similar outcomes as to long-term graft survival and complications compared with those of single renal artery. Renal artery multiplicity should not be a contraindication for live kidney donation and may not increase the risk of ureteral complications.

Influence of Dialysis Duration on the Outcome of Living Kidney Transplantation

Previous studies have reported negative impacts of long‐term dialysis on kidney transplantation (KTx) outcomes. However, advances in surgical techniques, immunosuppressive therapies, and post‐transplant monitoring have led to an impressive increase in patient and allograft survival. Thus, the number of KTx among patients on long‐term dialysis is increasing. We evaluated the influence of dialysis duration on the outcome of living donor KTx. Between January 2000 and October 2011, we performed 1098 first KTx from living donors in adults (>18 years). We divided the patients into six groups, A group: pre‐emptive kidney transplantation, B group: <24 months duration of dialysis, C group: 25–60 months duration, D group: 61–120 months duration, E group: 121–240 months duration, and F group: ≥241 months duration. The 5‐year patient survival rates were 95.7, 98.8, 99.0, 99.0, 97.3, and 100% in groups A–F, respectively. The 5‐year graft survival rates were 91.3, 95.6, 94.2, 96.3, 90.7, and 100% in groups A–F, respectively. No significant differences were observed in patient or graft survival among the six groups. Longer dialysis duration was correlated with lower rates of preoperative hypertension and diabetes mellitus. Survivors of long‐term dialysis tended to be in good compliance with self‐management. If recipients of living KTx have few complications, good prognoses are expectable even if dialysis periods are very long.

Novel approach for bladder cancer treatment using sulfoquinovosylacylpropanediol as a radiosensitizer

DOI: 10.1111/iju.13034 Several clinical guidelines have recommended optimal treatments for bladder cancer according to the clinical and pathological stage, and histological grade. Whereas transurethral resection is generally selected for patients with low-grade NMIBC, radical cystectomy should be carried out to manage muscle-invasive bladder cancer and high-grade NMIBC, including bacille Calmette–Gu erin-refractory NMIBC, depending on the patient’s performance status, age, comorbidity and other factors. Additionally, bladder-preserving strategies, such as XRT and chemotherapy, have been investigated as alternatives to radical cystectomy. However, XRTtreated patients occasionally experience severe adverse events as a result of radiation dose escalation, which might exceed 40 Gy. Accordingly, lower-dose XRT with a radiosensitizer is desirable, as it could prevent adverse events while yielding anticancer effects similar to conventional XRT. We recently reported that the novel XRT radiosensitizer, SQAP, enhanced growth inhibition in a xenotransplantation mouse model of human PCa. Our findings showed great potential for SQAP as a radiosensitizer in PCa through its ability to oxygenate tumor tissues by the induction of VN; additionally, the effect of tumor site oxygenation persisted at even 30 days after XRT + SQAP treatment. However, the radiosensitizing effects of SQAP in VN might have different outcomes according to the innate radiosensitivity of various tumors, and the mechanisms mediating the long-term effects of oxygenation with XRT + SQAP remain unclear. The two aims of the present study were therefore to evaluate: (i) the effect of VN with XRT + SQAP on bladder cancer; and (ii) the mechanisms mediating the long-term effects of oxygenation with XRT + SQAP. The study protocol is described in Figure 1a. This in vivo study was carried out in accordance with our facility’s Guidelines for Animal Experimentation (ID: 15–32). We obtained human bladder cancer cell lines, 5637 and UM-UC-3 (urinary bladder, epithelial, grade II carcinoma), as moderately radiosensitive cells, from the American Type Culture Collection (Manassas, VA, USA). Viable urinary bladder cancer cells (2 9 10) were injected subcutaneously into the right femurs of male BALB/c Slc-nude mice (aged 6–8 weeks). Once tumor volumes grew to 100–300 mm, 16 mice were divided into four groups based on mean tumor volumes (n = 4 each): control, SQAP alone, XRT alone and XRT + SQAP. Tumor volumes were measured regularly with calipers. Mice were killed for sample collection after 1 month. Immunofluorescent tumor staining was carried out to analyze tumor vessel radiosensitivity. To assess phenotypical tumor changes, such as vascular hyperpermeability after therapy, we labeled intravital blood vessels with tomato lectin and tumor vessel endothelial cells with a CD31-specific antibody, using a previously described procedure. The Mann–Whitney U-test was used for statistical comparisons of mean tumor volumes. Differences with P-values <0.05 were considered statistically significant. We attempted to evaluate the effects of a total 8-Gy dose of XRT + SQAP on 5637 and UM-UC-3 cells. However, we did not observe differences between the XRT alone and XRT + SQAP groups in both cells (Fig. S1a,b). Therefore, we reduced the total radiation dose to 4 Gy and evaluated the radiosensitizing effects of SQAP using only 5637 cells. The mean tumor volume was significantly smaller in the XRT + SQAP group than in the XRT alone group at each time-point (P < 0.05), whereas no significant effect was observed with SQAP alone (Fig. 1b). XRT + SQAP delayed tumor growth more effectively, and this effect persisted for more than 1 month after just two irradiation fractions for a total of 4 Gy. In accordance with the difference in tumor volumes at 1 month, in the XRT + SQAP group, only a few CD31 immunoreactive cells without lectin labeling were observed, whereas CD31 immunoreactive endothelial cells were abundant on tumor vessels, and lectin leakage remained visible in the XRT alone group and the control group (Fig. 1c). These findings suggest that XRT + SQAP normalizes tumor vessels, which leads to endothelial cell dysfunction, and this effect maintains for approximately 1 month.

Successful Kidney Transplantation for End-Stage Renal Disease in Marfan's Syndrome.

Marfans syndrome is a systemic disorder of the connective tissue caused by mutations in the extracellular matrix protein fibrillin-1, with aortic dissection and aneurysm being its most life-threatening manifestations. Kidney transplantation for end-stage renal disease (ESRD) in patients with Marfans syndrome has not been reported in the literature, and the rate of the incidence of dissection or aneurysm in the iliac artery is unknown. Here, we present a patient with Marfans syndrome with ESRD due to severe renal ischemia caused by massive bleeding from thoracoabdominal aortic dissection leading to transplant surgery of a living kidney procured from the patients mother. After kidney transplantation, the renal function normalized without vascular complications, and stable graft function along with negative results for both microhematuria and proteinuria continued for two years. Also, vascular complication such as aneurysm or dissection of the iliac artery was not observed using ultrasonography during the follow-up period. ESRD patients with Marfans syndrome might be suitable for kidney transplantation, but long-term and careful observations are needed.

Comprehensive Approach to Genetic Analysis and Therapy in Patient with Recurrence Atypical Hemolytic Uremic Syndrome: 998

Hemolytic uremic syndrome (HUS) is a disorder characterised by thrombotic microangiopathy (TMA) with thrombocytopenia, haemolytic anaemia and renal failure. Two different forms can be described. The typical form is usually associated with food-borne infections with Shigalike toxin producing Escherichia coli O157:H7 (E. coli O157:H7) causing diarrhea and in approximately 6% end-stage renal failure (ESRD); however, the long-term prognosis is good. Atypical HUS (aHUS), is most frequently seen in children and is not caused by infection with the toxin-producing E. coli. The prognosis is less favourable, up to 50% progress to ESRD. Uncontrolled activation of the complement system is related to the pathogenesis of aHUS, half of which accounts for the mutations of regulatory genes involved in the alternative pathway of the complement cascade including complement factor H (CFH), complement factor I (CFI), membrane cofactor protein (MCP or CD46), complement component 3 (C3), complement factor B (CFB), and thrombomodulin (THBD). Normal plasma levels of complement proteins do not preclude the presence of a mutation in these genes. More importantly, genotypephenotype correlations of aHUS have clinical significance in predicting renal recovery and transplant outcome. We describe an adult renal transplant recipient who developed recurrent hemolytic uremic syndrome 3 weeks after transplantation. The initial diagnosis before transplantation was diarrheal associated epidemic HUS without Shiga-like toxin. Due to proven episodes of HUS we suspected a possible dysfunctioning complement system which consequently was thoroughly investigated. Directional sequencing of CFH confirmed that the causative mutation inherited from paternal part in CFH has been detected in the patient with aHUS. The missense mutation of CFH is R1215Q localized in the vitally functional area of domain 20. The hemolysis test of sheep erythrocyte with the presentation of CFH purified protein is positive in this patient, which is a proof of dysfunctional CFH. Results of renal transplantation in patients with mutations in either CFH or CFI are dismal, with recurrent disease leading to graft loss in the majority of cases. However the patient with a factor H polymorphism was successfully transplanted with postoperative plasmapheresis and administration of eculizumab. This report reemphasizes the importance of screening patients with atypical hemolytic uremic syndrome for mutations in these genes before renal transplantation and shows the challenges in the management of these patients. 1006