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Background: Few studies have established that obesity promotes all types of urinary incontinence and disorders of the pelvic floor. The role of bariatric surgery in urinary incontinence remains poorly studied., Objective: To determine the effect of bariatric surgery on urinary incontinence, dysuria, and fecal incontinence before and 1 year after bariatric surgery., Setting: University hospital expert in bariatric surgery METHODS: This was an observational cohort study of 140 patients who underwent bariatric surgery between September 2013 and September 2014. Patients prospectively completed 4 questionnaires, 2 for urinary symptoms and 2 for fecal incontinence. Eighty-three women and 33 men completed 4 questionnaires the day before surgery when arriving in the department and 1 year after surgery., Results: Of the 140 patients, 116 completely responded to the 4 questionnaires. The rate of urinary incontinence was 50.9% before surgery and 19% at 1-year follow-up (P<.0001). After bariatric surgery, there was improvement in the rate of stress urinary incontinence: 39.7% before surgery versus 15.5% at 1 year (P<.0001). In addition, there was an improvement in urinary urge incontinence: 36.8% versus 7.9% at 1 year (P<.0001). The dysuria rate was 19.8% before surgery versus 3.4% at 1 year (P<.0001). Bariatric surgery improved the quality of life related to urinary symptoms (P<.0001). One year after surgery, there was no significant difference in terms of prevalence and severity of fecal incontinence., Conclusion: We confirmed with our study that weight loss after bariatric surgery improves stress urinary incontinence, urge incontinence, dysuria, and quality of life. However, we did not find any positive effect on fecal incontinence., (Copyright © 2017. Published by Elsevier Inc.)

Objective: 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., Design: 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., Setting: 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., Participants: 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., Results: There was no difference between junior and senior residents, whereas the registrars had better results (p < 0.0001). 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., Conclusion: 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., (Copyright © 2016 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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 7.4ng/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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Selective targeting of CD28 might represent an effective immunomodulation strategy by preventing T cell costimulation, while favoring coinhibition since inhibitory 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 allotransplantation. 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 calcineurin inhibitor (CNI)-low or CNI-free protocols, without the need of steroids. Accumulation of intragraft Tregs suggested the promotion of immunoregulatory mechanisms. Selective CD28 antagonists might become an alternative CNI-sparing strategy to B7 antagonists for kidney transplant recipients., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

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., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

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., (Copyright © 2012 Elsevier B.V. All rights reserved.)

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., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Acute antibody-mediated rejection is an unsolved issue in transplantation, especially in the context of pretransplant immunization. The deleterious effect of preformed cytotoxic anti-HLA antibodies through complement activation is well proven, but very little is known concerning complement blockade to prevent/cure this rejection. Here, we used a baboon model of preimmunization to explore the prevention of acute antibody-mediated rejection by an early inhibition of the classical complement pathway using human recombinant C1-inhibitor. Baboons were immunized against peripheral blood mononuclear cells from allogeneic donors and, once a specific and stable immunization had been established, they received a kidney from the same donor. Rejection occurred at day 2 posttransplant in untreated presensitized recipients, with characteristic histological lesions and complement deposition. As recombinant human C1-inhibitor blocks in vitro cytotoxicity induced by donor-specific antibodies, other alloimmunized baboons received the drug thrice daily intravenously during the first 5 days after transplant. Rejection was prevented during this treatment but occurred after discontinuation of treatment. We show here that early blockade of complement activation by recombinant human C1-inhibitor can prevent acute antibody-mediated rejection in presensitized recipients. This treatment could also be useful in other forms of acute antibody-mediated rejection caused by induced antibodies.