Sara Álvarez

Development of urologic de novo malignancies after renal transplantation.

OBJECTIVES The incidence of neoplasms in renal transplant recipients is higher than in general population. The increasing age of donors and recipients also increases the risk of developing malignancies, including genitourinary. The aim of this study is to analyze clinical aspects and management of this complication. MATERIALS AND METHODS We conducted a retrospective analysis of 1365 patients who underwent renal transplantation between 1977 and 2010 who were 44.6 ± 14.9 years old at the time of transplantation. The median follow-up was 95.6 months (range, 18.0-236.0). Data were analyzed for sex, age, time from transplant to diagnosis, location, clinical stage, immunosuppression, treatment, follow-up, and evolution. RESULTS We diagnosed 25 de novo urologic neoplasms (25/1365; 1.8%) in 24 patients, with a median follow-up of 32 months (range, 12.5-51.8) from the diagnosis. Sixteen were male (66.7%) and 8 female (33.3%), with a median age at diagnosis of 59 years (range, 56.0-65.5). The median time between the transplant and the diagnosis of the malignancy was 69 months (range, 40.0-116.5). There were 11 renal cell carcinomas (RCC; 11/25; 44%), 8 in native kidney and 3 in renal allograft; 9 prostate cancers (PCa; 9/25; 36%), 8 localized and 1 metastatic; and 5 transitional cell carcinomas (TCC; 5/25; 20%), 3 in bladder and 2 in renal allograft pelvis. Treatments performed were similar to those used in the nontransplanted population. RCC were treated with radical nephrectomy when affecting the native kidney, partial nephrectomy when affecting the allograft, or immunotherapy when metastatic. Patients with localized PCa were treated with radical prostatectomy, radiotherapy, or androgenic deprivation if there were comorbidities, and those metastatic with hormonal deprivation. Bladder TCCs were treated with transurethral resection or radical cystectomy. Pelvis TCCs affecting the allograft were treated with radical nephroureterectomy of the allograft including bladder cuff and pelvic lymphadenectomy. CONCLUSIONS There exists an increased incidence of urologic tumors in kidney transplant recipients. Conventional treatments of these tumors are technically feasible. The risk of developing these tumors remains even in the long term. Because of their suitability for curative treatments, it is advisable to perform periodic screening for urologic cancers to achieve an early diagnosis.

Transitional cell carcinoma of the kidney graft: an extremely uncommon presentation of tumor in renal transplant recipients.

Purpose. Transitional cell carcinoma (TCC) affecting the graft after renal transplantation is a very infrequent way of presentation of this tumor. Our aim is to present our single institution experience with 2 cases, as well as to perform a review of the literature about this tumor after the transplant. Materials and Methods. TCC of the graft developed in 2 of 1365 patients from 1977 to 2010, both cases in women. Data were analyzed for incidence, clinical presentation, treatment, and outcomes. Results. Both cases occurred in 2 mid-age women and resulted to be high grade and locally advanced TCCs, representing an incidence of 0,14% (2/1365). Clinical presentation was urinary obstruction for the first case and incidental ultrasound finding for the second. Preoperative staging was made with CT, cytology, pyelography, ureterorenoscopy, and biopsy. Treatment performed was nephroureterectomy of the graft with bladder cuff and regional lymphadenectomy. Pathological examination showed in both cases a locally advanced and high grade urothelial carcinoma of the pelvis allograft. After 24 and 14 months of followup, both patients are disease free. Conclusions. TCC of the kidney graft is an infrequent tumor that has only been reported in a few cases in the literature. It usually appears at a lower age, more often locally advanced, and with poor differentiation. A multidisciplinary approach to treatment should be required in these cases.

MP06-17 UROTHELIAL CARCINOMA AFTER KIDNEY TRANSPLANT: A HETEROGENEUS ENTITY IN TERMS OF DIAGNOSIS, TREATMENTS AND ONCOLOGICAL OUTCOMES

INTRODUCTION AND OBJECTIVES: Prostate cancer (PC) in renal transplant recipients (RTR) has not been widely studied and its incidence remains controversial, reported 2-5 times more than general population. The management of this disease is challenging because it is believed that RTR under immunosuppressive therapy may have increased postoperative morbidity and higher rate of tumor progression. Currently there are not guidelines or consensus about the management of this condition. The aim of the study was to analyze our experience in the management of PC in RTR. METHODS: Prospective and consecutive study in a single tertiary centre from 2003-2015. Inclusion of RTR diagnosed of PC by urinary symptoms, prostatic specific antigen (PSA), digital rectal examination, imaging and biopsies. PC assessment for staging and treatment was in agreement with the contemporary guidelines for the general population. Main outcome measures included demographics, characteristics and associated factors, type of treatment, complications, oncological outcomes and follow-up. Retrospective and descriptive analysis. RESULTS: During the study period 1330 renal transplants were performed, diagnosed of PC in 28 RTR (2.1%), mean age 66 years 6.6 (51-78). Type of donors were cadaveric (n1⁄426) and live (n1⁄42). Immunosuppressive therapy: without mTOR (n1⁄414) and with mTOR (n1⁄414). Mean time between renal transplantation and PC diagnosis 111 months 75 (24-270). Median PSA of 9.6ng/ml and PSA ratio 0.19. Treatment: a) Radical prostatectomy (n1⁄420): perineal approach (n1⁄416), laparoscopic (n1⁄42), robotics (n1⁄42)/ lymphadenectomy was performed in one patient; b) Radiotherapy combined with hormone therapy (n1⁄46); c) Active surveillance (n1⁄42). Histology: pT2 (n1⁄415), pT3a (n1⁄44) and pT3b (n1⁄41). No graft loss due to PC treatment was reported. Complications (18%): incontinence post-prostatectomy (n1⁄42), anastomotic stricture (n1⁄42) and urinary fistula (n1⁄41). Outcomes: Remission of the 85% (n1⁄422), Biochemical recurrence after radical prostatectomy treated with salvage radiotherapy (n1⁄44). Mortality by other causes without evidence of recurrence (n1⁄411), loss of monitoring (n1⁄41). Not specific mortality from cancer prostate was reported. Observed survival rates were 100% at 12 months after treatment. Mean follow-up was 61 months 37 (12-132). CONCLUSIONS: This is the first largest series to analyze the management of PC in RTR from a single center in Spain. PC after renal transplantation could be managed as any non-organ transplant patient with the same range of therapeutic options. According to our experience, these patients has similar histopathologic evaluation, posttreatment complications, rate of remission and recurrence than non-transplant patients, without specific mortality from PC. Active surveillance should also be provided in RTR despite being under immunosuppressive treatment.

MP06-20 RANDOMIZED EXPERIMENTAL STUDY COMPARING NON-OXYGENATED VS OXYGENATED HYPOTHERMIC MACHINE PERFUSION IN A TYPE III NON-HEART-BEATING DONOR PIG MODEL OF AUTOTRANSPLANTATION.

INTRODUCTION AND OBJECTIVES: Hypothermic machine perfusion (HMP) reduces risk of delayed graft function (DGF) and improves graft survival. Cold reduces oxygen requirement, although metabolic rate remains around 10% and consequently hypoxia would result a source of tissue damage. Hence, the concept of supplying O2 during perfusion is growing, because it would combine active circulation of dissolved oxygen in the perfusate. Oxygenated HMP could allow ATP resynthesis.The aim of the study was to compare HMP with or without oxygen in a pig model of kidney autotransplantation, reproducing conditions of type III non-heart-beating donor (NHBD) METHODS: Porcine model of type III NHBD autotransplantation approved by animal ethical committee. 6 female pigs randomized to HMP with or without O2. Left kidney retrieval after 30 min of warm ischemia time (WIT). Kidney was cold-flushed with Celsior and preserved in LifePort for 22 h. Afterward, nephrectomy of the remaining right kidney and the transplant of the preserved left kidney in an orthotopic manner were performed. Perfusion conditions are measured with serial perfusate gasometry and miRNAs expression, as well as hemodynamic machine parameters. Serum levels of creatinine are measured every 2 days. After sacrifice, pathology exam was carried out RESULTS: Fig. 1 shows Cr evolution, with a peak 2-3 days after transplant. Oxygenated HMP (pigs 1, 5, 6) has shown nearly significant differences in flow: 73.3 vs 46.7 (p1⁄4 0.05) and RI: 0.36 vs 0.54 (p1⁄40.05) at the end of perfusion. Fig. 1 shows histological analysis of kidneys and miR10a expression. The increased expression of miR10a (lower DCTs) that has been linked to cell proliferation and tubular repair is correlated with the presence of severe ATN in animal 2. CONCLUSIONS: In our preliminary results, oxygenated HMP has shown nearly significant differences in flow and RI at the end of perfusion, as well as better functional results. ATN development was linked to increased expression of miR10a that would make it a biomarker for graft outcome. Similarly, oxygenated allografts have shown lower miR10a expression correlating with less tissue damage, so they could be a useful tool for monitoring oxygen effects in kidney perfusion