Robot-assisted kidney transplantation with regional hypothermia using grafts with Multiple Vessels After Extracorporeal Vascular Reconstruction: results from the European Association of Urology Robotic Urology Section Working Group

Background: Kidney transplantation using grafts with multiple vessels (GMVs) is technically demanding and may be associated with increased risk of complications or suboptimal graft function. To date, no studies have reported on robot-assisted kidney transplantation (RAKT) using GMVs. Objective: To report our experience with RAKT using GMVs from living donors, focusing on technical feasibility and early postoperative outcomes. Design, setting, and participants: We reviewed the multi-institutional, prospectively collected European Association of Urology (EAU) Robotic Urology Section (ERUS)-RAKT database to select consecutive patients undergoing RAKT from living donors using GMVs between July 2015 and January 2018. Patients undergoing RAKT using grafts with single vessels (GSVs) served as controls. In case of GMVs, ex vivo vascular reconstruction techniques were performed during bench surgery according to the case-specific anatomy. Intervention: RAKT with regional hypothermia. Outcome measurements and statistical analysis: Intraoperative outcomes and early (30 d) postoperative complications and functional results were the main study endpoints. Multivariable logistic regression analysis evaluated potential predictors of suboptimal renal function at 1 mo. Results and limitations: Overall, 148 RAKTs were performed during the study period. Of these, 21/148 (14.2%) used GMVs; in all cases, single arterial and venous anastomoses could be performed after vascular reconstruction. Median anastomoses and rewarming times did not differ significantly between the GMV and GSV groups. Total and cold ischemia times were significantly higher in the GMV cohort (112 vs 88 min, p = 0.004 and 50 vs 34 min, p = 0.003, respectively). Overall complication rate and early functional outcomes were similar among the two groups. No major intra-or postoperative complications were recorded in the GMV cohort. At multivariable analysis, use of GMVs was not significantly associated with suboptimal renal function at 1 mo. Small sample size and short follow-up represent the main study limitations. Conclusions: RAKT using GMVs from living donors is technically feasible and achieved favorable perioperative and short-term functional outcomes. Larger studies with longer follow-up are needed to confirm our findings. Patient summary: In this study, we evaluated for the first time in literature the results of RAKT from living donors using kidneys with multiple arteries and veins. We found that, in experienced centers, RAKT using kidneys with multiple vessels is feasible and achieves optimal results in terms of postoperative kidney function with a low number of postoperative complications. (C) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved

Sphingosine Kinase-1 Is Central to Androgen-Regulated Prostate Cancer Growth and Survival

BACKGROUND: Sphingosine kinase-1 (SphK1) is an oncogenic lipid kinase notably involved in response to anticancer therapies in prostate cancer. Androgens regulate prostate cancer cell proliferation, and androgen deprivation therapy is the standard of care in the management of patients with advanced disease. Here, we explored the role of SphK1 in the regulation of androgen-dependent prostate cancer cell growth and survival. METHODOLOGY/PRINCIPAL FINDINGS: Short-term androgen removal induced a rapid and transient SphK1 inhibition associated with a reduced cell growth in vitro and in vivo, an event that was not observed in the hormono-insensitive PC-3 cells. Supporting the critical role of SphK1 inhibition in the rapid effect of androgen depletion, its overexpression could impair the cell growth decrease. Similarly, the addition of dihydrotestosterone (DHT) to androgen-deprived LNCaP cells re-established cell proliferation, through an androgen receptor/PI3K/Akt dependent stimulation of SphK1, and inhibition of SphK1 could markedly impede the effects of DHT. Conversely, long-term removal of androgen support in LNCaP and C4-2B cells resulted in a progressive increase in SphK1 expression and activity throughout the progression to androgen-independence state, which was characterized by the acquisition of a neuroendocrine (NE)-like cell phenotype. Importantly, inhibition of the PI3K/Akt pathway--by negatively impacting SphK1 activity--could prevent NE differentiation in both cell models, an event that could be mimicked by SphK1 inhibitors. Fascinatingly, the reversability of the NE phenotype by exposure to normal medium was linked with a pronounced inhibition of SphK1 activity. CONCLUSIONS/SIGNIFICANCE: We report the first evidence that androgen deprivation induces a differential effect on SphK1 activity in hormone-sensitive prostate cancer cell models. These results also suggest that SphK1 activation upon chronic androgen deprivation may serve as a compensatory mechanism allowing prostate cancer cells to survive in androgen-depleted environment, giving support to its inhibition as a potential therapeutic strategy to delay/prevent the transition to androgen-independent prostate cancer

Robot-assisted Kidney Transplantation: The European Experience.

BACKGROUND: Robot-assisted kidney transplantation (RAKT) has recently been introduced to reduce the morbidity of open kidney transplantation (KT). OBJECTIVE: To evaluate perioperative and early postoperative RAKT outcomes. DESIGN, SETTING AND PARTICIPANTS: This was a multicenter prospective observational study of 120 patients who underwent RAKT, predominantly with a living donor kidney, in eight European institutions between July 2015 and May 2017, with minimum follow-up of 1 mo. The robot-assisted surgical steps were transperitoneal dissection of the external iliac vessels, venous/arterial anastomosis, graft retroperitonealization, and ureterovesical anastomosis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive analysis of surgical data and their correlations with functional outcomes. RESULTS AND LIMITATIONS: The median operative and vascular suture time was 250 and 38min, respectively. The median estimated blood loss was 150ml. No major intraoperative complications occurred, although two patients needed open conversion. The median postoperative estimated glomerular filtration rate was 21.2, 45.0, 52.6, and 58.0ml/min on postoperative day 1, 3, 7, and 30, respectively. Both early and late graft function were not related to overall operating time or rewarming time. Five cases of delayed graft function (4.2%) were reported. One case (0.8%) of wound infection, three cases (2.5%) of ileus, and four cases of bleeding (3.3%; three of which required blood transfusion), managed conservatively, were observed. One case (0.8%) of deep venous thrombosis, one case (0.8%) of lymphocele, and three cases (2.5%) of transplantectomy due to massive arterial thrombosis were recorded. In five cases (4.2%), surgical exploration was performed for intraperitoneal hematoma. Limitations of the study include selection bias, the lack of an open control group, and failure to report on patient cosmetic satisfaction. CONCLUSIONS: When performed by surgeons with robotic and KT experience, RAKT is safe and reproducible in selected cases and yields excellent graft function. PATIENT SUMMARY: We present the largest reported series on robot-assisted kidney transplantation. Use of a robotic technique can yield low complication rates, rapid recovery, and excellent graft function. Further investigations need to confirm our promising data

Robotic kidney transplantation using right-versus left-sided grafts from living donors: an european multicentre experience (ERUS-RAKT working group)

Introduction: RAKT from living donors (LD) is increasingly performedin selected centers with experience in robotic surgery and kidneytransplantation (KT). Of note, KT from LD using right-sided graft (RSG)is challenging due to the brevity of the right renal vein and has beenassociated with a higher riskof perioperative complications in selectedseries. In this scenario, RAKT may facilitate the performance ofvascular anastomoses in case of short renal vessels thanks to theadvantages of the robotic platform. However, the evidence on thesafety and feasibility of RAKT using RSGs is lacking. The aim of thisstudy is to compare the surgical andearly perioperative outcomes after RAKT from LD using right- vs. left-sided grafts in a large prospectivemulticenter cohort (ERUS-RAKT working group)

[Self-retaining ureteric removal of an encrusted ureteric stent after 10 years].

International audienceAutostatic ureteral stents have been commonly used in urology for more than 20 years. Encrustation is a frequent and well described phenomenon that sometimes makes stent removal difficult. The main predisposing factors are: duration of stenting, history or concomitant stone disease, urinary tract infection or bacterial colonization, pregnancy and chemotherapy. Treatment depends on the degree of encrustation, especially when it involves the proximal loop. Extracorporeal lithotripsy alone or combined with endoscopic treatment is very effective, but open surgery may sometimes be necessary. The authors report a case in which drainage was exceptionally prolonged as the stent was removed after a period of 10 years. Stent removal required 3 operations, including one open procedure. The steps of treatment are described and the aetiologies of encrustation and the therapeutic strategy are discussed

Kidney transplantation during the COVID‐19 pandemic: Potential long‐term consequences of an early post‐transplant infection

International audienceRecently, Akalin et al.1 reported a 28% mortality among kidney‐transplant patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2). Two of the 10 patients who died had been transplanted within the previous 5 weeks. During the coronavirus disease (COVID)‐19 outbreak, kidney transplant programs were suspended in several countries2. Although the pandemic is still ongoing, the stop of lockdown has prompted several transplant centers to restart kidney transplantation programs. It is recommended to consider that donors and recipients are screened for SARS‐CoV‐2 before transplantation by means of nuclear acid tests with or without chest CT scans

Chemosensitizing effects of sphingosine kinase-1 inhibition in prostate cancer cell and animal models

We have previously reported that, in prostate cancer, inhibition of the oncogenic sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) pathway is a key element in chemotherapy-induced apoptosis. Here, we show that selective pharmacologic inhibition of SphK1 triggers apoptosis in LNCaP and PC-3 prostate cancer cells, an effect that is reversed by SphK1 enforced expression. More importantly, we show for the first time that the up-regulation of the SphK1/S1P pathway plays a crucial role in the resistance of prostate cancer cells to chemotherapy. Importantly, pharmacologic SphK1 inhibition with the B-5354c compound sensitizes LNCaP and PC-3 cells to docetaxel and camptothecin, respectively. In vivo, camptothecin and B-5354c alone display a limited effect on tumor growth in PC-3 cells, whereas in combination there is a synergy of effect on tumor size with a significant increase in the ceramide to S1P sphingolipid ratio. To conclude, our study highlights the notion that drugs specifically designed to inhibit SphK1 could provide a means of enhancing the effects of conventional treatment through the prosurvival antiapoptotic SphK1/S1P pathway

Impact of positive vascular margins status after surgical resection of non-metastatic renal cell carcinoma with caval tumour thrombus: a propensity score multicentre study

International audienceBackground Data evaluating the impact of positive vascular margins (PVMs) following surgical resection of non-metastatic renal cell carcinoma (RCC) with inferior vena cava (IVC) tumor thrombus are lacking. Objective To analyze the oncological impact of positive vascular margins following surgical resection of RCC with IVC tumor thrombus. Methods Patients who underwent radical nephrectomy with the removal of IVC tumour thrombus for RCC between 2000 and 2019 were included. PVMs were identified from pathology reports defined as microscopically identified tumour present in the IVC wall at the site of resection or in case of thrombus was not completely removed. To achieve balance in baseline characteristics between patients with PVMs versus negative vascular margins, we used inverse probability of treatment weighting (IPTW) based on the propensity score. Local recurrence, distant metastasis and overall mortality were evaluated between groups using Cox proportional hazards regression models. Results 209 patients were analyzed. Among them, 49 (23%) patients with PVMs were identified. Median follow-up was 55 months. After adjustment, excellent balance was achieved for most propensity score variables. In IPTW analysis, PVMs was associated with a higher risk of local recurrence (HR = 3.66; p < 0.001) without any impact on systemic recurrence (HR = 1.15; p = 0.47) or overall mortality (HR = 1.23; p = 0.48). Limitations include the sample size and unmeasured confounding. Conclusion Our results suggest that a PVMs in patients with RCC after nephrectomy with thrombectomy is associated with a higher risk of local recurrence, however, it did not appear to influence the risk of distant metastasis or death

Sphingosine kinase-1 activity and expression in human prostate cancer resection specimens

Sphingosine kinase-1 (SphK1) was shown in preclinical models and non-genitourinary cancers to be instrumental in cancer progression, adaptation to hypoxia and in tumour angiogenesis. No data were available in human prostate cancer. The present study was designed to assess SphK1 expression and activity in radical prostatectomy specimens and to research correlations with clinical features

Treatment of large plasma volumes using specific immunoadsorption to desensitize ABO-incompatible kidney-transplant candidates

Background: ABO-incompatible (ABOi) kidney-transplantation has very good long-term results, i.e. similar to those observed for living-kidney ABO-compatible transplantation. This is because patients are desensitized at pretransplant using apheresis and rituximab therapy, with tacrolimus-based immunosuppression. Objectives: To assess the efficacy of a single, pretransplant (Day –1), specific immunoadsorption session using Glycosorb® columns (anti-A or anti-B; Glycorex Sweden) to treat large volumes of plasma (up to 18 L). Patients and Methods: Prospective single-center study evaluating 12 consecutive patients (6 males), aged 40 (23–59) years. Incompatibilities were A into 0 (8), B into 0 (3), and AB into 0 (1). Pretransplant desensitization relied on rituximab (D–30), tacrolimus, mycophenolic acid, and steroids (all started on D–13), and a single session of specific immunoadsorption on D–1. Immunoadsorption was coupled in tandem with a hemodialysis session. Results: Overall, 15 L (11–18) of plasma were treated per patient, i.e., 0.2 (0.11–0.36 L/kg). Isoagglutinin titers were 1/16 (1/5–1/64) before the procedure, decreasing after 6 hours to 1/5 (1/1–1/16 P = 0.008), and to 1/2 (1/1–1/8; P = 0.05) at completion of the session. The next day, i.e., the day of transplantation, there was no rebound of isoagglutinins [1/4 (1/1–1/5); P = ns]. The procedure was well tolerated with no side-effects and no significant changes in hemoglobin level, platelet counts, fibrinogen, or albumin levels. Conclusions: For ABOi kidney-transplantation, a single, longer, specific immunoadsorption session was very efficient at 1-day pre-transplantation with no rebound. These results should be confirmed when isoagglutinin titers are higher (≥120)