Y. Tobisawa

BK Virus–Associated Urothelial Carcinoma of a Ureter Graft in a Renal Transplant Recipient: A Case Report

BACKGROUND Urothelial carcinomas of ureter grafts in renal transplant patients are rare. Here we report our experience with a case of BK virus-associated urothelial carcinoma in a ureter graft. CASE REPORT A 47-year-old man developed chronic renal failure secondary to diabetes mellitus and started maintenance hemodialysis in September 2007. Two months later, the patient received a renal transplant from his 70-year-old mother. The patient developed BK virus-associated nephropathy 1 year after transplantation and presented with a decline in renal function and hydronephrosis in the transplanted kidney 4 years 6 months after transplantation. Cystoscopy and retrograde pyelography revealed an irregular filling defect in the ureter graft. Cytologic diagnosis of his urine revealed a high-grade urothelial carcinoma. Computerized tomography showed a cT2 ureteral tumor and no involvement of other organs. The patient subsequently underwent a transplant nephroureterectomy with bladder cuff resection. Histopathologic findings revealed a high-grade urothelial carcinoma, pT2, in the ureter graft with SV40-positive staining. The patient was closely observed without adjuvant chemotherapy therapy and remained disease free 1 year after surgery. Renal transplant recipients with BK virus infection are at high risk of developing urologic malignancies. Close attention is necessary to diagnose post-transplantation urologica malignancies as early as possible.

604 Serum N-glycan profiling predict antibody mediated rejection in patients undergoing living kidney transplantation

INTRODUCTION AND OBJECTIVES: With the development of living donor nephrectomy in recent years, the surgical management of nephrectomy has also evolved. Standard laparoscopic donor nephrectomy (SLDN) has been largely developed, nevertheless the robotassisted approach is not widespread in this indication. The objective of this study was to compare perioperative outcomes between SDN and robot-assisted laparoscopic donor nephrectomy (RALDN). METHODS: Between 2003 and 2015, in two academic centres, all patients who underwent a donor nephrectomy by SLDN (group A) or RALDN were compared. We assessed patient’s characteristics and perioperative outcomes including: type of surgery, operating time, warm ischemia time, complications and hospital length of stay. Comparison betweens groups were performed using c2 test and Fisher exact test for discrete variables and Mann-Whitney test for continuous variables. RESULTS: We included 277 patients, 226 in the SLDN group and 51 in the RaLDN. Mean age was similar in both groups (51 years vs. 52 years, p1⁄40.59), as mean BMI (25.1 kg/m2 vs. 25.6kg/m2; p1⁄40.39). Groups were also comparable for ASA score (ASA 1: 79% vs. 82%; p1⁄40.66), side of nephrectomy (Left in 94% vs. 88%; p1⁄40.12) in group A and B respectively. Study of perioperative outcomes, revealed a longer operating time in the RaLDN (143 min vs. 233min; p<0.001), and a longer warm ischemia time (3.5 min vs. 6.2min; p<0.001). Hospital length of stay was shorter in the RaLDN group (5.7 days vs. 5.1 days; p1⁄40.006). Complications rate was similar in both groups (p1⁄40.66). Only one hemorrhagic complication occurred in group B (surgeon at the beginning of the learning curve) requiring a transfusion. CONCLUSIONS: Robot-assisted laparoscopic living donor nephrectomy is feasible, operating time and warm ischemia time are longer but hospital length of stay is shorter. Complications rate is similar with SDN, nevertheless it is necessary to perform this procedure once the learning curve of robotic surgery passed. Long-term data on the receiver are needed to confirm the feasibility of RALDN.

243 Glycan modification of podoplanin enhances growth factor production through stabilization of platelet aggregation in bladder cancer cell

INTRODUCTION AND OBJECTIVES: Non-muscle invasive bladder cancer is often treated by intravesical chemotherapy following transurethral resection. Mechanism of the effect of intravesical chemotherapy has yet to be elucidated. In this study, we investigated cell death mechanism induced by high-dose chemotherapeutics using a newly-developed culture method for primary cancer cells. METHODS: We have developed a novel culture method which enables preparation and culture of primary cancer cells as multicellular spheroids which are termed cancer tissue-originated spheroids (CTOSs) (Okuyama 2013 J Urol). First we generated a bladder cancer patient-derived xenograft. We prepared CTOSs from the xenograft, and exposed to high-dose (1mg/ml) of epirubicin (e-ADM) or mitomycin C (MMC) for 2 hours, or low-dose (0.01mg/ml) of those chemotherapeutics. We investigated absorption of chemotherapeutics into CTOSs and assessed the mode of cell death. Next, we prepared CTOSs directly from surgical specimens of bladder cancer and tested the individual responses after exposure to high-dose e-ADM and MMC. RESULTS: At high dose, e-ADM was promptly and homogenously delivered into cancer cells in the CTOSs. High-dose e-ADM and MMC decreased ATP levels in CTOSs within an hour accompanied with mitochondrial swelling and reduction of mitochondrial membrane potential, while plasma membrane integrity was maintained. Some of the molecules in mitochondrial apoptotic pathway were subsequently activated, while at later time point the cells lost integrity of cell membrane without DNA laddering. In contrast, CTOSs exposed to low-dose of eADM or MMC exhibited typical DNA laddering. Intriguingly, the decrease of ATP levels was varied among CTOSs derived from 20 surgical specimens. CONCLUSIONS: High-dose chemotherapeutics used in intravesical therapy may induce necrosis-like cell death, different from typical apoptosis caused by chemotherapeutics at the dose of systemic chemotherapy. Each bladder cancer may have a different response to high-dose chemotherapeutics used in intravesical therapy, indicating necessity of chemosensitivity test aiming for personalized medicine.