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Summary Aim Secondary uretero-arterial fistulas (SUAF) are uncommon, underrated and threatening for any patient. Gross hematuria is a clinical symptom of this pathology for patients with history of pelvic radiotherapy, complex pelvic surgery or long-term ureteral stenting. The purpose of this work is to assess risk factors, diagnosis and treatment of SUAF. Methods Monocentric and retrospective series of 6 new cases illustrated by a literature review through MedLine and Pubmed using the keywords “arterio-ureteral fistula”, “arterio iliac fistula” and “ilio-ureteral fistula”. We excluded uretero-arterial fistula following vascular surgery. Results Our series included 4 men and 2 women. All patients had a history of complex pelvic surgery and long-term ureteral stenting. Three patients had history of pelvic radiotherapy. They all had inaugural macroscopic haematuria episode. Two fistula cases were diagnosed on 5 repeated CT-scans. In 2 out of 5 cases, arteriography highlighted the fistula. Fistulas were generally located at the left common iliac artery. An endovascular stent was placed in 5 out of 6 cases. One patient needed open surgery. After treatment, 3 patients remained alive, 3 patients died either by a fistula relapse or by complications late in the treatment. Conclusion SUAF are uncommon, but serious. Today, there is no specific recommendation regarding complex treatment of these fistulas. Endovascular stents seem to be a good therapeutic option. Level of proof 3.

OBJECTIVE To propose recommendations for the management of renal cell carcinomas (RCC) of the renal transplant. METHOD Following a systematic approach, a review of the literature (Medline) was conducted by the CTAFU to evaluate prevalence, diagnosis and management of RCC arousing in the renal transplant. References were assessed according to a predefined process to propose recommendations with levels of evidence. RESULTS Renal cell carcinomas of the renal transplant affect approximately 0.2% of recipients. Mostly asymptomatic, these tumors are mainly diagnosed on a routine imaging of the renal transplant. Predominant pathology is clear cell carcinomas but papillary carcinomas are more frequent than in general population (up to 40-50%). RCC of the renal transplant is often localized, of low stage and low grade. According to tumor characteristics and renal function, preferred treatment is radical (transplantectomy) or nephron sparing through partial nephrectomy (open or minimally invasive approach) or thermoablation after percutaneous biopsy. Although no robust data support a switch of immunosuppressive regimen, some authors suggest to favor the use of mTOR inhibitors. CTAFU does not recommend a mandatory waiting time after transplantectomy for RCC in candidates for a subsequent renal tranplantation when tumor stage

Characteristics of renal carcinoma arising in non-functional graft in renal transplant recipients (RTR) are unknown. We studied a large national retrospective cohort to analyze circumstances of diagnosis, treatment and outcome compared to the literature. Study included all RTR presenting with kidney graft tumors irrespective of the histology, except those with lymphoma and including those tumors arising in non-functional renal graft. Between January 1988 and December 2018, 56,806 patients had renal transplantation in the 32 centers participating in this study. Among this cohort, 18 renal graft tumors were diagnosed in non-functional grafts. The median patient age at the time of diagnosis was 42.1 years (31.7–51.3). Median age of kidney grafts at the time of diagnosis was 56.4 (23.2–63.4). Eight (44.4%) tumors were discovered fortuitously on renal graft histologic analysis. Fourteen tumors (77.8%) were papillary carcinomas. Two patients had clear cell carcinomas and one patient had a pTa high-grade multifocal urothelial carcinoma in the graft of the upper tract with an in situ carcinoma. Renal carcinomas in non-functional grafts are rare entities and most of them are diagnosed fortuitously. Despite the fact that these tumors are small, low grade and with a good prognosis, regular monitoring of non-functional grafts should be performed with at least an annual ultrasonography.

To evaluate the residual cancer rate after cystoprostatectomy (CPT) in patients with a history of radiation therapy for prostate cancer and the postoperative complication rates. We conducted a retrospective study involving 21 patients who had a CPT over 7 years and who had a history of radiotherapy for prostate cancer. To compare results, two additional groups were created: a group of patients without a history of radiotherapy in whom a CPT was performed, and a group without a history of radiotherapy and in whom was accidentally discovered a prostate cancer after CPT on histology specimens. The median age at the time of radiotherapy was 69 years. The median age at the time of cystoprostatectomy was 78 years. The median PSA at the time of the intervention was 0.6 ng/ml in the group with a history of radiotherapy. The residual cancer rate was 24%. No patients had criteria for biological recurrence. There were no additional surgical complications in the radiotherapy group (p = 0.2). The rate of cutaneous ureterostomy was higher (p = 0.0006) due to increased surgical difficulties (p = 0.0009). The residual cancer rate was 24% after radiotherapy for prostate cancer. PSA alone does not appear to be sufficient to detect the persistence of residual prostate cancer after radiotherapy. There were no more surgical complications after prostate radiotherapy.

Prostate cancer (PC) is the most common neoplasia in men. With aging of solid organ transplant recipients (SOTR), its incidence is likely to increase. The aim of this study was to analyze PC screening results retrospectively in renal transplant recipients (RTR), hepatic transplant recipients (HTR) and cardiac transplant recipients (CTR). A retrospective monocentric study of PC diagnosed in renal, hepatic or cardiac transplanted patients since 1989 was performed. All the patients were followed annually by digital rectal examination and prostate serum antigen (PSA) dosage. 57 PC were diagnosed in 1565 SOTR male patients (3.6%): 35 RTR, 15 HTR, and 7 CTR. Standard incidence ratio (SIR) was 41.9. Mean age at the time of diagnosis was 64.5 (60.5–69.2). Mean time between transplantation and PC diagnosis was 95.7 (39.0–139.5) months. Median PSA rate was 7.0 (6.2–13) ng/mL. Clinical stages were T1, T2, and T3, respectively, for 29, 22 and 6 patients. Diagnosis was done by screening in 52 patients, after prostatitis in 1 and bone pain in another. Three PC were discovered on prostate chips after transurethral resection. Two patients were treated by active surveillance. 39 (68%) patients (25 RTR, 11 HTR and 3 CTR) were treated by radical prostatectomy. Histological results were 30 pT2 and 9 pT3 tumors, with 7 positive surgical margins. Gleason score was 5, 6, 7, 8 and 9 in, respectively, in 2, 24, 11, 1 and 1 patients. One patient with positive pelvic nodes was treated with hormonal therapy (HT). One had a biochemical relapse at 10 months and underwent salvage radiotherapy. Median follow-up was 85.2 months (46.1–115.0). 23 (40.4%) patients died. Two (3.6%) RTR and 1 (1.8%) CTR died from their PC. Standard incidence ratio were, respectively, 42.4, 48.2 and 39 in RTR, HTR and CTR. Systematic screening in male SOTR after 50 years old could not be recommended. In the last 3 decades, we diagnosed too many low-risk prostate cancers strongly increasing the SIR but failing to decrease prostate cancer related mortality. SOTR should undergo individual screening with prior MRI when PSA rates are high. Management should not be different from that of the general population.

Introduction: The benefit of adjuvant radiotherapy (AR) or salvage radiotherapy (SR) after prostatectomy is still unclear. We wanted to compare both types of radiotherapy after prostatectomy in terms of oncological and functional results. Methods: We included 173 patients treated at a single center between January 2005 and December 2008. All patients were treated with the same radiotherapy protocol (3D conformal radiotherapy accelerator 6 mV, 66 GY). AR was defined as radiotherapy initiated in a patient with a PSA level 10%. Both groups were compared in terms of biological progression-free, metastasis-free, and overall survival (OS) using log-rank tests. Moreover, acute and late urinary and gastrointestinal toxicity were also compared. Results: One hundred and fifty-seven patients underwent an open retropubic prostatectomy whereas 16 underwent a laparoscopy (6 subperitoneal and 10 transperitoneal). Eighty-six patients had AR with a median time of 6.7 months after surgery and 87 had SR with a median time of 21.4 months after surgery. Median follow-up was 6.7 years. Metastasis-free survival (MFS) was better in the AR than in the SR group (p = 0.01, 6-year MFS 95 and 89%, respectively). OS was also better in the AR than in the SR group (p = 0.02, 6-year OS 100 vs. 95%, respectively). AR was associated with better survival with no biochemical recurrence (85 vs. 63%, p < 0.00001). There was no significant difference between groups for acute or late urinary or gastrointestinal toxicity. Conclusion: Our study suggests that patients treated by AR have better results in terms of OS, disease-specific survival, survival without metastatic recurrence, and survival without biochemical recurrence compared with SR. Toxicity was comparable between both groups.

Face, content, and construct validity of robotic surgery simulators were confirmed in the literature by several studies, but elements to build a training program are still lacking. The aim of our study was to validate a progressive training program and to assess according to prior surgical experience the amount of training needed with a robotic simulator to complete the program.Exercises using the Da Vinci Skill Simulator were chosen to ensure progressive learning. A new exercise could only be started if a minimal score of 80% was achieved in the prior one. The number of repetitions to achieve an exercise was not limited. We devised a "performance index" by calculating the ratio of the sum of scores for each exercise over the number of repetitions needed to complete the exercise with at least an 80% score.The study took place at the François Baclesse Cancer Center. Participants all work at the primary care university Hospital located next to the cancer center.A total of 32 surgeons participated in the study- 2 experienced surgeons, 8 junior and 8 senior residents in surgery, 6 registrars, and 6 attending surgeons.There was no difference between junior and senior residents, whereas the registrars had better results (p0.0001). The registrars performed less exercise repetitions compared to the junior or senior residents (p = 0.012). Attending surgeons performed significantly more repetitions than registrars (p = 0.024), but they performed fewer repetitions than junior or senior residents with no statistical difference (p = 0.09). The registrars had a performance index of 50, which is the best result among all novice groups. Attending surgeons were between senior and junior residents with an index at 33.85.Choice of basic exercises to manipulate different elements of the robotic surgery console in a specific and progressive order enables rapid progress. The level of prior experience in laparoscopic surgery affects outcomes. More advanced laparoscopic expertise seems to slow down learning, surgeons having to "unlearn" to acquire a new technique.

Kidney transplantation in small animals has been crucial in the development of anti-rejection therapies. While there is no substitute for a skilled microsurgeon, there are many aspects of the transplant procedure that can be modified to optimize the reproducibility and utility of the technique. This article provides a detailed description, including video recording, of orthotopic kidney transplantation in the rat. The key variables in the technique are also discussed.

While either pancreas or pancreatic islet transplantation can restore endogenous insulin secretion in patients with diabetes, no beta-cell replacement strategies are recommended in the literature. For this reason, the aim of this national expert panel statement is to provide information on the different kinds of beta-cell replacement, their benefit-risk ratios and indications for each type of transplantation, according to type of diabetes, its control and association with end-stage renal disease. Allotransplantation requires immunosuppression, a risk that should be weighed against the risks of poor glycaemic control, diabetic lability and severe hypoglycaemia, especially in cases of unawareness. Pancreas transplantation is associated with improvement in diabetic micro- and macro-angiopathy, but has the associated morbidity of major surgery. Islet transplantation is a minimally invasive radiological or mini-surgical procedure involving infusion of purified islets via the hepatic portal vein, but needs to be repeated two or three times to achieve insulin independence and long-term functionality. Simultaneous pancreas-kidney and pancreas after kidney transplantations should be proposed for kidney recipients with type 1 diabetes with no surgical, especially cardiovascular, contraindications. In cases of high surgical risk, islet after or simultaneously with kidney transplantation may be proposed. Pancreas, or more often islet, transplantation alone is appropriate for non-uraemic patients with labile diabetes. Various factors influencing the therapeutic strategy are also detailed in this report.

The occurrence of a kidney transplant tumor is a rare but serious issue with a double risk: the return to dialysis and the development of metastatic cancer. Publications on this topic are mainly case reports. The purpose of this review was to report an exhaustive literature review of functional graft renal cell carcinomas to highlight the impact of tumors on the renal graft outcomes. 201 de novo renal carcinomas in functional renal grafts from 69 publications were included. Incidence was estimated at 0.18%. Graft tumors were mostly asymptomatic (85.9%). Whatever the discovery circumstances of graft tumors, they were mostly documented by graft ultrasounds supplemented by CT-scanning or MR imaging. Nephron sparing surgery (95 patients) was the first treatment performed followed by radiofrequency ablation (38 patients) and cryotherapy (10 patients). The most common tumor graft histology was clear cell carcinoma (46.4%), followed by papillary carcinoma (43.7%). Specific mortality was 2.9% with 6 deaths. Renal graft cell carcinoma is a rare pathology with a low specific death. When possible, conservative treatment should be the first choice.

International audience; PURPOSE:Urolithiasis is rare among renal transplant recipients and its management has not been clearly defined.METHODS:This multicentre retrospective study was organised by the Comité de Transplantation de l'Association Française d'Urologie (French Urology Association transplantation committee). Statistical analysis was performed with SPSS 19 software.RESULTS:Ninety-five patients were included in this study. Renal transplant urolithiasis was an incidental finding in 55% of cases, mostly on a routine follow-up ultrasound examination. One half of symptomatic stones were due to urinary tract infection and the other half were due to an episode of acute renal failure. The initial management following diagnosis of urolithiasis was double J stenting (27%), nephrostomy tube placement (21%), or watchful waiting (52%). Definitive management consisted of: watchful waiting (48%), extracorporeal lithotripsy (13%), rigid or flexible ureteroscopy (26%), percutaneous nephrolithotomy (11%) and surgical pyelotomy (2%). All transplants remained functional following treatment of the stone. The main limitation is the retrospective design.CONCLUSIONS:The incidence of lithiasis could be higher in kidney transplanted patients due to a possible anatomical or metabolical abnormalities. The therapeutic management of renal transplant urolithiasis appears to be comparable to that of native kidney urolithiasis.

To determinate feasibility and results of the flush technique by hands for the surgical management of renal cell carcinoma (RCC) with levels III and IV inferior vena cava thrombus (VCT). We conducted a retrospective study for all patients who underwent a surgical treatment for RCC with levels III and IV VCT in our department between June 2010 and July 2017. Sixteen patients were identified. All tumors were resected using a subcostal incision for right RCC and a chevron incision for the left RCC. Vena cava control was performed only on its subhepatic portion. After renal artery ligature, anesthesiologists were asked to generate a positive pressure in the small circulation. Subsequently, the vena cava was incised longitudinally to the orifice of the renal vein and the thrombus dissected and extracted of the upper part of the vena cava. Only once the supra-renal part of the vena cava was free of thrombus, the supra-renal portion of the vena cava could be clamped. We never had to perform neither thoracotomy nor hepatic mobilization. Therefore, support of a hepatic, vascular or cardiac surgeon was not necessary. The mean operative time was 201 min. The mean estimated blood loss was 2040 ml. No patient died during hospitalization, and mean hospitalization stay duration was 16.6 days. The flush technique allows a limitation of the dissection extent. It requires neither hepatic mobilization nor thoracotomy. This results in a decrease in the operative time and blood loss.

Although we have seen revolutionary changes with multi-disciplinary management of patients with rectal cancer, the evaluation of genito-urinary sequelae remains of great concern. Precise pre-operative evaluation with validated scores allows detection of urinary disorders in 16 to 23% of patients, and sexual disorders in nearly 35% of men and 50% of women. Regardless of the surgical approach, it is fundamental to respect the autonomic innervation during total mesorectal excision in order to prevent these sequelae. Identification of these nerves can be facilitated by intra-operative neuro-stimulation. In spite of these precautions, de novo urinary sequelae are observed in nearly 33% of patients and bladder evacuation disorders in 25% of patients. Advanced age, pre-operative urinary disorders, female gender, and abdomino-perineal resection are independent risk factors for urinary sequelae. Early post-operative urodynamic abnormalities might be predictive of these sequelae and justify early physiotherapy. Likewise, sexual sequelae such as erectile and/or ejaculatory disorders, dyspareunia and lubrication deficits result in de novo cessation of sexual activity in 28% of men and 18% of women. Advanced age, neo-adjuvant radiation therapy, and abdomino-perineal resection are independent risk factors for sexual dysfunction. Pharmacotherapy with sildenafil has proven useful in the treatment of erectile disorders. Genito-urinary and ano-rectal sequelae occur concomitantly in more than one of ten patients, suggesting a potential common pathophysiology.

Aims: To evaluate a simple and fast technique to ensure negative surgical margins on partial nephrectomies, while correlating margin statuses with the final pathology report. Subjects and Methods: This study was conducted for patients undergoing partial nephrectomy (PN) with T1–T2 renal tumors from January 2010 to the end of December 2015. Before tumor removal, intraoperative ultrasound (US) localization was performed. After tumor removal and before performing hemostasis of the kidney, the specimens were placed in a saline solution and a US was performed to evaluate if the tumor's capsule were intact, and then compared to the final pathology results. Results: In 177 PN(s) (147 open procedures and 30 laparoscopic procedures) were performed on 147 patients. Arterial clamping was done for 32 patients and the mean warm ischemia time was 19 ± 6 min. The mean US examination time was 41 ± 7 s. The US analysis of surgical margins was negative in 172 cases, positive in four, and in only one case it was not possible to conclude. The final pathology results revealed one false positive surgical margin and one false negative surgical margin, while all other margins were in concert with US results. The mean tumor size was 3.53 ± 1.43 cm, and the mean surgical margin was 2.8 ± 1.5 mm. Conclusions: The intraoperative US control of resection margins in PN is a simple, efficient, and effective method for ensuring negative surgical margins with a small increase in warm ischemia time and can be conducted by the operating urologist.

Summary Introduction The surgical issues of renal transplantation (RT) after localized prostate cancer (PC) treatment and oncological outcomes after transplantation in patients on the waiting list with a history of PC were unknown. We conducted a retrospective multicentre study including all patients with PC diagnosed before the kidney transplantation. Methods Fifty-two patients were included from December 1993 to December 2015. The median age at diagnosis of PC was 59.8 years old. Results The median PSA rate at diagnosis was 7 ng/mL. Twenty-seven, Twenty-four, and one PC were respectively low, intermediate and high risk according to d’Amico classification. Forty-three patients were treated by radical prostatectomy (RP): 28 retropubic, 15 laparoscopic and 3 by a perineal approach. Eighteen patients had a lymph node dissection. Four patients were treated with external radiotherapy and 2 by brachytherapy. Eight patients underwent radiotherapy after surgery. The median time between PC treatment and RT was 35.7 months. The median operating time for the renal transplantation was 180 min (IQR 150–190; min 90–max 310) with a median intraoperative bleeding of 200 mL (IQR 100–290; min 50–max 2000). A history of lymphadenectomy did not significantly lengthen operative time ( P = 0.34). No recurrence of PC was observed after a median follow of 36 months. Conclusion PC discovered before RT should be treated with RP to assess the risk of recurrence and decrease waiting for a RT. If the PC is at low risk of recurrence, it seems possible to shorten the waiting time before the RT after a multidisciplinary discussion meeting. Level of evidence 4.

To determine the impact of non-functional renal graft nephrectomy on second kidney transplantation survival.We performed a retrospective study on patients managed in our department from April 1989 to April 2011. We compared the number of acute graft rejections and graft survival between patients undergoing second transplantation with (Group I) or without (Group II) prior graft nephrectomy.A total of ninety-one patients received a second renal graft: 43 underwent graft nephrectomy and 48 kept their non-functional renal graft. There were 5 episodes of acute graft rejection in Group I and 12 in Group II (p = 0.3). Six (13.9 %) grafts failed in Group I and eight (16.6 %) in Group II. Five and 10 years actuarial graft survival in Group I were, respectively, 91 and 85 %, while in Group II were 82.7 % and 69 % (p = 0.2). PRA level and number of acute rejection episodes did not have a statistically significant influence on graft survival, whether the patient had a nephrectomy or not (p = 0.2).Nephrectomy of a failed allograft did not significantly improve the survival of a subsequent graft. Graft nephrectomy should be indicated in case of graft-related pain or a chronic inflammation syndrome.

Summary Background: Our objective was to clarify the clinical outcome of renal transplantation based on residual daily urine output (RDUO). Material/Methods: We retrospectively analyzed a prospective database of 276 patients who underwent renal transplantation (Tx) between January 2008 and December 2012. Patients had pre-transplantation daily urine output measurement of 24-h proteinuria and were clinically re-evaluated the day before transplantation. We included patients with no daily urine output and those with residual daily urine output. Real bladder capacity was not measured. We excluded patients with a history of lower urinary tract malformation, those treated by trans-ileal conduit or enterocystoplasty, and those with early graft thrombosis or graft primary non-function. Results: Sex ratio, age at Tx, pre-Tx MHC antibodies levels, donor age, and cold ischemia duration were not significantly different between the 2 groups. Dialysis duration was longer in group I (p

Background The objective of this study is to explore the impact of PSA nadirs on detection rates of prostate cancer (PCa) recurrence with 18F-choline (CH) PET/CT after external beam radiation therapy (EBRT). Methods In this retrospective study, data were collected from 54 patients with suspicion of PCa biochemical recurrence after EBRT (28 patients treated initially with EBRT and 26 as salvage therapy in the absence of PSA decrease after initial treatment), who underwent 18F-CH PET/CT between 2010 and 2015. PSA nadir and trigger PSA were collected from patient files. Relative PSA was calculated by subtracting the nadir from the trigger PSA. Results Median PSA nadir was 0.31 (0.01–13.31) ng/mL, trigger PSA was 7.85 (0.47–111.60) ng/mL, and relative PSA was 6.05 (0.24–104.59) ng/mL. Overall, 40 (74%) PET/CT scans were positive: recurrence was local and/or regional in 29 patients, distant in 15 and combined both in four, with no association between PSA values and sites of recurrence. In univariate analysis, trigger (p = 0.015) and relative (p = 0.0005) PSA values and PSA velocity (p = 0.01) were significantly linked to positive PET/CT, but PSA nadir was not. In subgroup analysis, these significant differences were only found in the salvage EBRT group. Akaike Information Criterion multivariate model comparison found that relative PSA was a better predictor of positive PET/CT than trigger PSA (PSAt). 18F-CH PET/CT detection rates increased with trigger and relative PSA: 0% (0/4 patients), 71% (5/7 patients), and 81% (35/43 patients) for PSAt 4 ng/mL, respectively, and 14% (1/7 patients), 50% (5/10 patients), and 92% (34/37 patients) when relative PSA was taken into account instead of trigger PSA, with seven (13%) patients changing subgroups. Conclusions We found a high overall detection rate and an increase in detection rates proportional to trigger and relative PSAs. Although relative PSA, taking into account PSA nadir, was a better predictive factor of PET/CT positivity in univariate analysis, this was most noticeable for high PSAs. For low PSAs, trigger PSA remains most relevant. Larger series with intermediate PSA values need to be studied to fully apprehend nadir impact.

International audience; BACKGROUND:Results of the conservative treatment of renal cell carcinomas arising in functional renal transplants are unknown compared to transplant nephrectomy. Only small series or case reports have been reported.METHODS:Data were collected from 32 transplantation centers nationwide on cases of de novo tumors in functional renal transplants presumed to be malignant between January 1988 and December 2013.RESULTS:Among 116 de novo transplant tumors, 62 were treated conservatively including: 48 by partial nephrectomy (PN) and 14 by thermal ablation (TA). These patients were compared to 30 other patients who were treated by transplant nephrectomy. The median age of the transplanted kidneys at the time of diagnosis was 43.5 years old as calculated from the donor's age. Tumors treated by transplant nephrectomy presented more often with symptoms (pain, fever, impaired condition, hematuria) than tumors treated conservatively (P = .019). After PN, final histology showed 27 (47.5%) papillary carcinomas, 19 (32.2%) clear cell carcinomas, 1 mixed carcinoma, and 2 oncocytomas. The median tumor size treated by PN was 24 mm with no difference in comparison to the TA group. Nine patients treated by PN had postoperative complications (21%), including 4 requiring operative intervention (Clavien IIIb). None of the patients treated by TA had complications. Specific survival was 100% at the time of last follow-up (median time after treatment 37 months) for patients treated by PN or TA.CONCLUSION:PN proved to be efficient in the treatment of small tumors of transplanted kidneys with good long-term functional and oncologic outcomes, including avoiding return to dialysis. TA seems to be an alternative therapy with good results in selected patients.

Galactosyl-transferase knockout (GT-KO) pigs represent the latest major progress to reduce immune reactions in xenotransplantation. However, their organs are still subject to rapid humoral rejection involving complement activation requiring the ongoing development of further genetic modifications in the pig. In a pig-to-baboon renal transplantation setting, we have used donor pigs that are not only GT-KO, but also transgenic for human CD55 (hCD55), hCD59, hCD39, and fucosyl-transferase (hHT). We studied kidney xenograft survival, physiological and immunologic parameters, xenogeneic rejection characteristics, as well as viral transmission aspects among two groups of baboons: control animals (n = 2), versus those (n = 4) treated with a cocktail of cyclophosphamide, tacrolimus, mycophenolate mofetil, steroids, and a recombinant human C1 inhibitor. Whereas control animals showed clear acute humoral rejection at around day 4, the treated animals showed moderately improved graft survival with rejection at around 2 weeks posttransplantation. Biopsies showed signs of acute vascular rejection (interstitial hemorrhage, glomerular thrombi, and acute tubular necrosis) as well as immunoglobulin (Ig)M and complement deposition in the glomerular and peritubular capillaries. The low level of preformed non-Gal-α1.3Gal IgM detected prior to transplantation increased at 6 days posttransplantation, whereas induced IgG appeared after day 6. No porcine endogenous retrovirus (PERV) transmission was detected in any transplanted baboon. Thus, surprisingly, organs from the GT-KO, hCD55, hCD59, hCD39, and hHT transgenic donors did not appear to convey significant protection against baboon anti-pig antibodies and complement activation, which obviously continue to be significant factors under a suboptimal immunosuppression regimen. The association, timing, and doses of immunosuppressive drugs remain critical. They will have to be optimized to achieve longer graft survivals.

Objective To describe a simple method for ensuring surgical margins during laparoscopic partial nephrectomy (PN). Materials and Method A study was done at our institution from October 2013 to March 2014 for all patients undergoing laparoscopic PN for T1 renal tumors. Before tumor removal, intraoperative ultrasonography (US) localization was performed. The tumor was then removed with a standardized minimal healthy tissue margin technique. Immediately after removal and before performing hemostasis of the kidney, the specimen was placed into a laparoscopic endobag filled with saline solution. The laparoscopic probe was then placed into the endobag and a sequential ultrasonographic scan was performed to evaluate if the tumor's pseudocapsule was respected. Results Twelve patients were included in our study. Mean warm ischemia time was 19 ± 3 minutes. Mean US examination was 42 ± 9 seconds. US analysis of surgical margins was negative in all except 1 patient. The final histologic examination of all specimens confirmed US results with a 100% correlation. Conclusion We describe an original, simple, and cost-effective method for ensuring surgical margins during laparoscopic PN with a moderate increase in warm time ischemia.

International audience; Objectives To evaluate the oncological outcomes of papillary renal cell carcinoma (pRCC) following nephron sparing surgery (NSS) and to determine whether the subclassification type of pRCC could be a prognostic factor for recurrence, progression, and specific death. Materials and methods An international multicentre retrospective study involving 19 institutions and the French network for research on kidney cancer was conducted after IRB approval. We analyzed data of all patients with pRCC who were treated by NSS between 2004 and 2014. Results We included 486 patients. Tumors were type 1 pRCC in 369 (76 %) cases and type 2 pRCC in 117 (24 %) cases. After a mean follow-up of 35 (1–120) months, 8 (1.6 %) patients experienced a local recurrence, 12 (1.5 %) had a metastatic progression, 24 (4.9 %) died, and 7 (1.4 %) died from cancer. Patients with type I pRCC had more grade II (66.3 vs. 46.1 %; p \textless 0.001) and less grade III (20 vs. 41 %; p \textless 0.001) tumors. Three-year estimated cancer-free survival (CFS) rate for type 1 pRCC was 96.5 % and for type 2 pRCC was 95.1 % (p = 0.894), respectively. Three-year estimated cancer-specific survival rate for type 1 pRCC was 98.4 % and for type 2 pRCC was 97.3 % (p = 0.947), respectively. Tumor stage superior to pT1 was the only prognostic factor for CFS (HR 3.5; p = 0.03). Conclusion Histological subtyping of pRCC has no impact on oncologic outcomes after nephron sparing surgery. In this selected population of pRCC tumors, we found that tumor stage is the only prognostic factor for cancer-free survival

International audience; Objective - Evaluate the feasibility of laparoscopic nephrectomy for big tumors. Material and methods - Data from 116 patients were retrospectively collected from 16 tertiary centres. Clinical and operative parameters, tumor characteristics, pre- and postoperative parameters, and renal function before and after surgery were analyzed. Results - Mean age and body mass index were 61 years and 27.8 kg/m(2), respectively. Males represented 63.8% of patients, and 54.4% presented symptoms at diagnosis. Median tumor size was 11 cm, and 75% of the cases were performed by expert surgeons. Median operative time and blood loss were 180 minutes and 200 mL respectively. Conversion to open surgery was necessary in 20.7% of cases. Intraoperative complications related to massive hemorrhage occurred in 16.4% of patients, resulting in open conversion in 62.5%. Major postoperative complications occurred in only 10 patients (8.6%). In univariate analysis, intraoperative complications, age, and blood loss were predictive factors of conversion to open surgery. Positive surgical margins occurred in 6 patients (5.2%). None of them presented a local recurrence. Predictive factors of recurrence or progression were lymph node invasion, metastases, and Furhman grade. Conclusion - Laparoscopic nephrectomy for tumors > 10 cm can be performed safely. Complication rate and positive surgical margins are similar to open surgery. In experienced hands, the benefit of a mini invasive surgery remains evident.

Objectives: To analyze retrospectively our series of prostate cancer (PC) in liver transplant recipients (LTRs) given an increase in frequency in an aging recipient population when no studies were reported in literature. Methods: We conducted a retrospective analysis of LTRs in a single institution. After liver transplantation, all patients were followed up in our institution with an annual digital rectal examination by a urologist and prostate-specific antigen measurement after the age of 50 years. Results: Between 1995 and 2013, among 361 male LTRs, 12 (3.3%) had PC. The mean age at diagnosis was 62.8 years, and the time lapse between liver transplantation and diagnosis was 55.7 months. The median initial prostate-specific antigen level was 7.4 ng/ml. In total, 9 patients underwent radical prostatectomy. Histological findings showed 5 pT2 and 4 pT3 cancers. A patient showed invasion in the lymph nodes and was treated with hormonotherapy. Another patient had a biochemical recurrence at 10 months and underwent salvage radiotherapy. After 32.9 months of follow-up, no other patients showed any recurrence. Moreover, 1 patient was treated by radiohormonotherapy for high-risk PC with no recurrence at 65 months, and 1 patient was treated with high-intensity focal ultrasound. There was 1 patient with metastatic disease who received hormonotherapy and died 5 months after diagnosis. Conclusion: Our incidence of intermediate- and high-risk PCs in LTRs was slightly higher than in the general population. In the absence of any recommendations, individual screening should be proposed to LTRs. The treatment of choice remains surgery or radiotherapy to ensure a good carcinologic control. r 2015 Elsevier Inc. All rights reserved.

International audience; Selective targeting of CD28 might represent an effective immunomodulation strategy by preventing T cell costimulation, while favoring coinhibition since inhib-itory signals transmitted through CTLA-4; PD-L1 and B7 would not be affected. We previously showed in vitro and in vivo that anti-CD28 antagonists suppress effector T cells while enhancing regulatory T cell (Treg) suppression and immune tolerance. Here, we evaluate FR104, a novel antagonist pegylated anti-CD28 Fab' antibody fragment, in nonhuman primate renal allo-transplantation. FR104, in association with low doses of tacrolimus or with rapamycin in a steroid-free therapy, prevents acute rejection and alloantibody development and prolongs allograft survival. However , when FR104 was associated with mycophenolate mofetil and steroids, half of the recipients rejected their grafts prematurely. Finally, we observed an accumulation of Helios-negative Tregs in the blood and within the graft after FR104 therapy, confirmed by Treg-specific demethylated region DNA analysis. In conclusion , FR104 reinforces immunosuppression in calci-neurin inhibitor (CNI)-low or CNI-free protocols, without the need of steroids. Accumulation of intra-graft Tregs suggested the promotion of immunoregu-latory mechanisms. Selective CD28 antagonists might become an alternative CNI-sparing strategy to B7 antagonists for kidney transplant recipients.

Galactosyl-transferase KO (GalT-KO) pigs represent a potential solution to xenograft rejection, particularly in the context of additional genetic modifications. We have performed life supporting kidney xenotransplantation into baboons utilizing GalT-KO pigs transgenic for human CD55/CD59/CD39/HT. Baboons received tacrolimus, mycophenolate mofetil, corticosteroids and recombinant human C1 inhibitor combined with cyclophosphamide or bortezomib with or without 2-3 plasma exchanges. One baboon received a control GalT-KO xenograft with the latter immunosuppression. All immunosuppressed baboons rejected the xenografts between days 9 and 15 with signs of acute humoral rejection, in contrast to untreated controls (n = 2) that lost their grafts on days 3 and 4. Immunofluorescence analyses showed deposition of IgM, C3, C5b-9 in rejected grafts, without C4d staining, indicating classical complement pathway blockade but alternate pathway activation. Moreover, rejected organs exhibited predominantly monocyte/macrophage infiltration with minimal lymphocyte representation. None of the recipients showed any signs of porcine endogenous retrovirus transmission but some showed evidence of porcine cytomegalovirus (PCMV) replication within the xenografts. Our work indicates that the addition of bortezomib and plasma exchange to the immunosuppressive regimen did not significantly prolong the survival of multi-transgenic GalT-KO renal xenografts. Non-Gal antibodies, the alternative complement pathway, innate mechanisms with monocyte activation and PCMV replication may have contributed to rejection.

BACKGROUND Surgical difficulties of renal transplantation related to prostate cancer (PC) treatment and the results of renal transplantation after radical prostatectomy are currently poorly known, as well as oncological follow-up before and after renal transplantation. MATERIAL/METHODS We performed a retrospective study including all patients diagnosed with PC before renal transplantation in our department. RESULTS Nineteen patients were included between August 2003 and December 2013. The mean age at diagnosis of PC was 61.7 years (range 51.4-71.1). PSA mean level at diagnosis was 8.5 ng/ml (range 4.8-20). Fourteen had a retro-pubic and 5 a laparoscopic prostatectomy. Three patients underwent radiotherapy for positive surgical margins or extra-capsular extension. Fourteen patients were transplanted. The mean time lapse between prostatectomy and kidney transplantation was 32.8 months (range 14-71). Seven recipients (50%) were transplanted less than 24 months after prostatectomy. Post-transplantation surgical complications were not significantly related to dissection difficulties (p=0.2). No recurrence of PC was observed after renal transplantation, with a mean follow-up of 38 months (range 6-77.9). CONCLUSIONS Prostate cancer discovered before renal transplantation should be treated by radical prostatectomy to assess recurrence risk. If the PC is at low risk of recurrence, it seems possible to shorten the 2-year period of oncologic follow-up before transplantation called for in current recommendations.

Objective. To evaluate the success of ureteral stent placement to treat or prepare for surgical treatment of urologic complications after renal transplantation, according to a type of ureteral anastomosis. Patient and methods. From May 1989 to December 2006, we performed 703 kidney transplantations including 412 extravesical ureteroneocystostomy (according to Lich-Gregoire technique) and 265 transvesical ureteroneocystostomy (according to Politano-Leadbetter technique). We retrospectively analyzed our endoscopic management of urinary leaks and ureteral strictures. The criteria of success were the feasibility to place a ureteral stent, permitting good drainage of the upper renal graft tract before further endoscopic or surgical treatment. Results. Forty-three urinary leaks or ureteral strictures occurred after extravesical ureteroneocystostomy (n = 21) or after Politano-Leadbetter anastomosis (n = 22). The success rate of endoscopic management was 75% (n = 16) for Politano-Leadbetter anastomosis versus 53% (n = 11) for the Lich-Gregoire anastomosis. There was no statistical difference (P = .1). Conclusion. Ureteroneocystostomy according to Lich-Gregoire procedure were twice less complicated than those according to the Politano-Leadbetter technique, but were associated with a rate of failure of ureteral stent placement in urgency higher to 25%.

International audience; Nephron sparing surgery (NSS) results in the transplanted population remain unknown because they are only presented in small series or case reports. Our objective was to study renal sparing surgery for kidney graft renal cell carcinomas (RCC) in a multicenter cohort. Data were collected from 32 French transplantation centers. Cases of renal graft de novo tumors treated as RCC since the beginning of their transplantation activity were included. Seventy-nine allograft kidney de novo tumors were diagnosed. Forty-three patients (54.4%) underwent renal sparing surgery. Mean age of grafted kidneys at the time of diagnosis was 47.5 years old (26.1-72.6). The mean time between transplantation and tumor diagnosis was 142.6 months (12.2-300). Fifteen tumors were clear cell carcinomas (34.9%), and 25 (58.1%) were papillary carcinomas. Respectively, 10 (24.4%), 24 (58.3%) and 8 (19.5%) tumors were Fuhrman grade 1, 2 and 3. Nine patients had postoperative complications (20.9%) including four requiring surgery (Clavien IIIb). At the last follow-up, 41 patients had a functional kidney graft, without dialysis and no long-term complications. NSS is safe and appropriate for all small tumors of transplanted kidneys with good long-term functional and oncological outcomes, which prevent patients from returning to dialysis.

Background Blockade of costimulation signaling required for immune response, such as CD40/CD40L and CD28/B7, is a reasonable strategy to prevent rejection and in defined combinations may allow donor specific tolerance. Indeed, in rodents, costimulation blockade with CD28/B7 antagonists or with CD40Ig was able to induce regulatory T cells and transplant tolerance whereas in primates, anti-CD40 antibodies, anti-CD40L antibodies or CTLA4Ig, used as monotherapy, significantly delayed graft rejection. Methods Using an adeno-associated virus (AAV) vector mediated gene transfer of a human CD40Ig fusion protein (hCD40Ig) in primates, we evaluated the capacity of this costimulation blockade molecule interfering with CD40/CD40L signaling in prolonging kidney transplants in cynomolgus monkeys. Results This gene transfer strategy allowed for maintaining a plateau of hCD40Ig production within two months and avoided a high-scale production phase of this molecule. Although the hCD40Ig was able to bind efficiently to human and macaque CD40L and high (> 200 μg/ml) transgene expression was obtained, no effect on graft survival was observed. In addition, there was no inhibition of humoral response to vaccination. In vitro , hCD40Ig strongly increased mixed lymphocyte reaction, and when compared to the anti-CD40L antibody h5C8, was not as potent to induce complement-dependent cytotoxicity. Conclusion These data suggest that CD40/CD40L blockade using a non-depleting CD40Ig fusion protein, a therapeutic strategy that showed efficacy in rodents, is not able to modulate the immune response in primates. These data highlight important biological differences between rodent and primate models to evaluate therapeutic strategies at the preclinical level.

Even if surgical complications are higher than in general population, overall survival in obese kidney recipients is better than in obese dialyzed patients with a body mass index up to 35 [2]. Moreover, third and fourth KT is becoming commonplace [3]. Surgical techniques are various in the literature. Some authors use a trans-peritoneal midline incision others use a retroperitoneal heterotopic approach. The overall surgical complications rate is about 25% without graft loss reported. Now we have come to fifth KT in patients whose life expectancy lengthens and in whom the progress of immunosuppression allows re-transplantation [4].

This article addresses an important and current subject in the field of renal transplantation. To retain a previous allograft before a second transplantation remains controversial despite several previous studies. Studies in the literature did not show that the nephrectomy of a failed allograft significantly influences the survival of a subsequent graft. In recent studies, Schleicher et al. observed a negative influence of primary allograft nephrectomy on the second transplant outcome. They further found that a lower donor age and delayed retransplantation after nephrectomy might improve results. Sumrani et al. also reported that primary allograft nephrectomy, by increasing PRA levels, could be detrimental to the new transplant. In contrast, an analysis of 127 retransplant patients by Douzdjian et al. found that despite the association of primary allograft nephrectomy with higher preformed antibody levels, regraft survival was not influenced by nephrectomy. In the present study, as in those of many other teams, the authors chose to remove the first renal transplant because of a graft intolerance syndrome or an acute rejection. Fadli et al. concluded that transplant nephrectomy is not a risk factor of increased retransplant failure. They confirmed the conclusions of the most recent studies dealing with the same subject. The decision to remove or retain a failed graft in the context of retransplantation should be based on known clinical indications for the procedure. However, the authors did not take into account other characteristics of the recipients waiting for a second transplantation. The decision to remove or retain a failed graft should also be based on an expected time to retransplantation, depending on the recipient’s blood type and level of sensitization. Chronic inflammation decreases hemoglobin levels, and blood transfusion must be avoided before transplantation. To leave a previous graft in patients with a potentially long duration of dialysis could compromise a second transplantation. Chronic inflammation related to the retained allograft could also lead to severe denutrition, which has a negative impact on any surgical procedure, such as renal transplantation. Allograft nephrectomy should not be restricted to patients with graft-related symptoms, but should be discussed while taking into account recipient age, expected time on the waiting list and the biological impact of the retained graft.

De novo tumors in renal allografts are rare and their prevalence is underestimated. We therefore analyzed renal cell carcinomas arising in renal allografts through a retrospective French renal transplant cohort. We performed a retrospective, multicentric survey by sending questionnaires to all French kidney transplantation centers. All graft tumors diagnosed after transplantation were considered as de novo tumors. Thirty-two centers participated in this study. Seventy-nine tumors were identified among 41 806 recipients (Incidence 0.19%). Patients were 54 men and 25 women with a mean age of 47 years old at the time of diagnosis. Mean tumor size was 27.8 mm. Seventy-four (93.6%), 53 (67%) and 44 tumors (55.6%) were organ confined (T1-2), low grade (G1-2) and papillary carcinomas, respectively. Four patients died of renal cell carcinomas (5%). The mean time lapse between transplantation and RCC diagnosis was 131.7 months. Thirty-five patients underwent conservative surgery by partial nephrectomy (n = 35, 44.3%) or radiofrequency (n = 5; 6.3%). The estimated 5 years cancer specific survival rate was 94%. Most of these tumors were small and incidental. Most tumors were papillary carcinoma, low stage and low grade carcinomas. Conservative treatment has been preferred each time it was feasible in order to avoid a return to dialysis.

Objective To evaluate the epidemiology, diagnosis, and outcome of de novo renal cell carcinoma in renal transplant recipients. Patients and Methods From June 1989 to August 2006, 800 renal transplant recipients were followed up annually by a urologist using abdominal ultrasonography or computed tomography. Renal lesions considered suspect were treated using extended nephrectomy. Incidence, diagnosis, histologic type, treatment, and outcome were analyzed in all patients. Results Thirty-three patients underwent nephrectomy because of suspect renal lesions including 22 de novo tumors in 21 native kidneys (renal clear-cell carcinoma in 15 and papillary carcinoma in 7). All tumors were classified as pT1aN0M0. Mean (range) time after diagnosis was 25.6 (2.3–105.5) months. Only 1 patient died, at 8 months after diagnosis. All other patients were alive at follow-up of 34.8 (2.8–113.9) months. Five-year survival was 92%. Conclusion The increased risk of tumor in renal transplant recipients leads us to propose extended nephrectomy in the case of suspect lesions in the native kidney. In our patients, 65% of patients had malignant lesions. Good prognosis for these localized tumors justified aggressive therapy even though 35% of transplant recipients were tumor-free.

International audience; OBJECTIVES: To evaluate the morbidity and surgical complications of retropubic radical prostatectomy (RRP) in renal transplant recipients (RTRs) and compare these results with the observed morbidity in a control group of nontransplanted patients. METHODS: We conducted a multicenter retrospective study and reviewed the charts and records of 20 RTRs who had undergone RRP for localized prostate cancer at four French renal transplant centers belonging to the Renal Transplantation Committee of the French Urological Association from April 1996 to April 2007. A total of 40 patients who had undergone RRP at the same centers, by the same surgeons, were analyzed as the case-control population. RESULTS: The mean operating time (163 +/- 41 vs 160 +/- 66 minutes), blood loss (516 +/- 279 vs 566 +/- 449 mL), transfusion rate (20% vs 22.5%), and hospital stay (11.9 +/- 5.44 vs 9.45 +/- 2.8 days) were similar in the RTR and case-control populations. No graft loss or graft injury was reported in the RTRs, except for two ureteral injuries that were immediately repaired during RRP. No decrease in the kidney graft function was observed after RRP. The rate of medical complication (deep venous thrombosis, pulmonary embolism, urinary tract infection) was similar in both groups, except for the rate of bacterial systemic infection, which was significantly greater in the RTRs than in the controls (15% vs 2.5%, P = .01). CONCLUSIONS: In our study, RRP was a safe procedure to treat localized prostate cancer in RTRs. RRP resulted in the same morbidity in RTRs as in the case-control population.

If single adrenal metastasis surgery is well admitted, no recommendation exists about the management of a renal vein tumor thrombus, even though the actual consensual attitude consists in a nephrectomy associated to an adrenalectomy. We report, here, the case of a 74-year-old man with a suspected adrenal metastasis of a lung carcinoma associated with a left adrenal and renal vein tumor thrombus treated by adrenalectomy and renal vein thrombectomy and ipsilateral kidney sparing. The postoperative computed tomography scan showed no thrombus in the left renal vein. Doppler ultrasound performed 1 month after adrenalectomy proved a good left renal vein flux. At 36 months of follow-up, the patient is alive without signs of recurrence.