[Urethro-vesical anastomosis reconstruction using extra-peritoneal robot-assisted laparoscopy for anastomotic stenosis after radical prostatectomy]. / Réfection d'anastomose urétro-vésicale par voie extra-péritonéale laparoscopique robot-assistée pour sténose anastomotique post-prostatectomie radicale.

INTRODUCTION: Urethro-vesical anastomosis stenosis following radical prostatectomy is a rare complication but represents a challenging situation. While the first-line treatment is endoscopic, recurrences after urethrotomies require a radical approach. We present the updated results of our patient's cohort treated by pure robotic anastomosis refection. MATERIAL AND METHODS: This is a retrospective, single-center study focusing on one surgeon's experience. Patients presented an urethro-vesical stricture following a radical prostatectomy. Each patient received at least one endoscopic treatment. The procedure consisted of a circumferential resection of the stenosis, followed by a re-anastomosis with well-vascularized tissue. We reviewed the outcomes in terms of symptomatic recurrences and continence after the reconstructive surgery. RESULTS: From April 2013 to May 2020, 8 patients underwent this procedure. Half of the patients had previously been treated with salvage radio-hormonotherapy. The median age was 70 years (64-76). The mean operative time was 109minutes (60-180) and blood loss was 120cc (50-250). One patient had an early postoperative complication, with vesico-pubic fistula. The average length of stay was 4.6 days (3-8). Mean follow-up was 24.25 months (1-66). Half of the patients experienced a recurrence at a median time of 8.25 months (6-11) after surgery. Five patients experienced incontinence of which 3 required an artificial urinary sphincter implantation. CONCLUSION: Extra-peritoneal robot-assisted urethro-vesical reconstruction is feasible and safe to manage bladder neck stricture after radical prostatectomy. The risk of postoperative incontinence is high, justifying preoperative information. LEVEL OF EVIDENCE: III.

[When to introduce hormone therapy after total prostatectomy with positive lymph nodes? Study of the factors influencing the time of introduction of hormone therapy]. / Quand introduire une hormonothérapie après prostatectomie totale avec curage ganglionnaire positif ? Étude des facteurs influençant le délai d'introduction de l'hormonothérapie.

INTRODUCTION: Adjuvant hormone therapy is the standard treatment after total prostatectomy with positive lymph node. However, this treatment has side effects and at the time of the PSA era and extensive lymph node dissection, this principle is questioned. The aim of this study is to describe the oncological characteristics of patients that may explain the delay in introducing hormone therapy in patients with positive lymph node. METHODS: Monocentric, retrospective study of 161 patients from November 1988 to February 2018 in a single French University Hospital, having undergone radical prostatectomy with positive lymph nodes on pathology. For each patient, preoperative data (age, clinical stage, biopsy results, d'Amico classification) and postoperative data (pathological results, number of lymph nodes removed, number of positive lympnodes, recurrence free survival, specific survival and overall survival) were collected. The date of introduction of hormone therapy was noted and survival without hormonal therapy was established according to the Kaplan Meier curve. The pre- and post-operative oncological factors that could influence hormone therapy introduction were investigated with Chi2 and Student tests (statistically significant when P<0.05). RESULTS: The mean number of lymph nodes removed was 12 [1-40]. The mean number of positive lymph nodes was 2.5 [1-24], the mean percentage of positive lymph nodes was 25% (2.5-100). After a mean follow-up of 95 months (3-354), 88 patients (54.6%) had no hormonal treatment. The average time to hormonal treatment was 40 months [0-310]. At 3 years, survival without hormone therapy was 52% and 51% at 5 years. Only the percentage of positive lymphnodes appeared to be a significant predictor of the introduction of hormone therapy. (29.32% vs. 21.99%, P=0.047). Hormone-free survival was significantly higher in patients with lymph node involvement less than 25% (P<0.0001) or with less than 2 positive lymph nodes (P=0.0294). CONCLUSION: Lymph node invasion is a factor of poor prognosis after total prostatectomy and leads to introduce hormone therapy. Our study identified the percentage and number of positive lymph nodes as factors that identify patients who may be delayed in introducing this hormone therapy. LEVEL OF PROOF: 3.

[Evaluation of single kidney graft outcome in patients initially programmed for a dual kidney graft transplantation]. / Évaluation de greffons de bigreffe transplantés en monogreffe.

INTRODUCTION: Kidney transplantation is championed as the gold standard treatment for patients with end-stage kidney disease. According to the biomedical agency, there is an increasing number of patients waiting for kidney transplantation. Faced with organ shortage, the use of marginal grafts may well increase the number of available kidney grafts. Occasionally, during dual kidney graft transplantation, the poor quality of one of the two grafts, or other specific circumstances, may lead to transplantation of only one of the two grafts. We have compared patient outcome concerning single kidney transplantation from an initial dual kidney graft with respect to dual kidney graft transplantation. MATERIAL: Among 67 patients enrolled for a dual kidney graft, 39 dual kidney grafts (group 1) were compared with 12 grafts performed with only one of the two kidneys of a dual kidney graft (group 2) as well as 15 grafts performed following a classic kidney graft protocol (group 3). RESULTS: The survival of grafts was respectively for groups 1, 2 and 3 of 100%, 72,5% and 75,4% (P=0.17). The survival of patients was respectively for groups 1, 2 and 3 of 78.3%, 89.9% and 87.8% (P=0.47). CONCLUSION: Our study suggests that transplantation of a single kidney, initially proposed as dual kidney graft candidate, has satisfying results in terms of graft survival and patient mortality at the expense of poorer renal function in comparison to dual kidney graft. Indeed, there was no significant difference in the survival of patients and grafts. This seems promising taking into consideration that the aim of transplantation in elderly recipients is primarily to avoid dialysis, rather than having optimal post-transplantation kidney function. LEVEL OF EVIDENCE: 4.

[Impact of neoadjuvant chemotherapy on the peri-operative morbidity of radical cystectomy for muscle invasive bladder cancer]. / Impact de la chimiothérapie néoadjuvante sur la morbidité péri-opératoire de la cystectomie pour tumeur de vessie infiltrant le muscle.

INTRODUCTION: Platinum-based neoadjvant chemotherapy (NAC) before radical cystectomy (RC) is the gold standard in the treatment of muscle invasive bladder cancer (MIBC). We aimed to compare the peri-operative morbidity in patients treated by NAC then RC and patients having RC alone. METHODS: Between 1st January 2008 and 31st December 2015, we retrospectively included consecutive patients undergoing RC for MIBC in 2centers. We collected clinical, pathological and peri-operative data (30day post operative complications according to the Clavien-Dindo score, delayed complications, pathological results). Patients treated by NAC (NAC-RC group) before RC were compared to patients performing RC alone. The NAC-RC group received 1 to 6cycle of high-dose MVAC, MVAC or gemcitabine-cisplatine chemotherapy. Logistic regression identified independant factors of peri-operative complications. RESULTS: We included 199 patients: 48in the NAC-RC group and 151in the RC group. Complications rate was 73.9% in the NAC-RC group versus 73.8% in the RC group (P=1.0). In multivariate analyses, only the Charlson score was associated with an increased risk of peri-operative complications (P=0.05). PT0 tumour rate was significantly higher in the NAC-CR group (50% vs 7%, P<0.001). CONCLUSION: NAC does not increase the peri-operative morbidity of the RC. Patients' pre operative comorbidities is the main risk factor for peri-operative complications.

Tumor heterogeneity of fibroblast growth factor receptor 3 (FGFR3) mutations in invasive bladder cancer: implications for perioperative anti-FGFR3 treatment.

BACKGROUND: Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer. Preclinical studies show that anti-FGFR3 treatment slows down tumor growth, suggesting that this tyrosine kinase receptor is a candidate for personalized bladder cancer treatment, particularly in patients with mutated FGFR3. We addressed tumor heterogeneity in a large multicenter, multi-laboratory study, as this may have significant impact on therapeutic response. PATIENTS AND METHODS: We evaluated possible FGFR3 heterogeneity by the PCR-SNaPshot method in the superficial and deep compartments of tumors obtained by transurethral resection (TUR, n = 61) and in radical cystectomy (RC, n = 614) specimens and corresponding cancer-positive lymph nodes (LN+, n = 201). RESULTS: We found FGFR3 mutations in 13/34 (38%) T1 and 8/27 (30%) ≥T2-TUR samples, with 100% concordance between superficial and deeper parts in T1-TUR samples. Of eight FGFR3 mutant ≥T2-TUR samples, only 4 (50%) displayed the mutation in the deeper part. We found 67/614 (11%) FGFR3 mutations in RC specimens. FGFR3 mutation was associated with pN0 (P < 0.001) at RC. In 10/201 (5%) LN+, an FGFR3 mutation was found, all concordant with the corresponding RC specimen. In the remaining 191 cases, RC and LN+ were both wild type. CONCLUSIONS: FGFR3 mutation status seems promising to guide decision-making on adjuvant anti-FGFR3 therapy as it appeared homogeneous in RC and LN+. Based on the results of TUR, the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. We conclude that studies on the heterogeneity of actionable molecular targets should precede clinical trials with these drugs in the perioperative setting.

[Retroperitoneal fibrosis in adults: Main characteristics and relevance of the diagnostic procedures based on a retrospective multicenter study on 77 cases]. / Fibrose rétropéritonéale de l'adulte : analyse descriptive et évaluation de la pertinence des examens complémentaires réalisés à visée diagnostique à partir d'une série rétrospective multicentrique de 77 cas.

INTRODUCTION: Retroperitoneal fibrosis (RPF) is a rare disorder characterized by the sheathing of retroperitoneal structures by fibro-inflammatory process. It can be either isolated or associated with an underlying disease or condition. In the absence of consistent and consensual approach, the objective of this study was to assess the relevance of diagnostic tests performed during the diagnostic work-up of RPF. METHODS: Seventy-seven patients were included in this retrospective multicenter study. The diagnosis of RPF was defined by the presence of a thickened circumferential homogeneous tissue unsheathing the infrarenal aorta, excluding peri-aneurysmal fibrosis and a clear evidence of a cancer. RESULTS: In 62 cases (80.5%), the RPF was considered as being primary or "idiopathic". Surgical (n=31) or CT-guided (n=9) biopsies of the RPF were performed in half of the patients showing some fibrotic or non-specific inflammatory lesions in 98% of cases. A bone marrow biopsy was performed in 23 patients leading to diagnosis of low grade B cell non-Hodgkin lymphoma in a single patient who also had a monoclonal gammopathy IgM. The systematic search for autoantibodies or serum tumor markers was of no diagnostic value. CONCLUSIONS: Although the diagnostic procedure was heterogeneous, no cause or associated disease was found in the majority of cases of FRP in this series. In the absence of any clinical or paraclinical evidence suggesting an underlying disease or any atypical features at presentation, a number of non-invasive tests (autoantibodies, tumor markers, bone scintigraphy) and also more invasive diagnostic tests (bone marrow and RPF biopsies) seem of little relevance.

[Oncological outcome of radical cystectomy for BCG failure compared to primary invasive disease]. / Résultats oncologiques de la cystectomie pour carcinome urothélial résistant au BCG comparés aux tumeurs invasives d'emblée.

INTRODUCTION AND OBJECTIVES: BCG therapy deeply modified prognosis of high-risk non muscle invasive (NMI) urothelial carcinomas. However, these tumors remain potentially lethal. The objective of this study was to compare oncological outcome of radical cystectomy (RC) for BCG failure to primary invasive (PI) tumors. MATERIAL AND METHODS: RC performed between 2001 and 2011 were retrospectively reviewed. Clinicopathological and follow-up data were compared between RC performed for: NMI high-grade recurrence under BCG therapy (ReNMI); MI recurrence (≥ T2) under BCG therapy (ReMI); primary invasive tumors (PI). The three groups were defined according to tumor status on last TUR before RC. All NMI high-grade bladder tumors at diagnosis had maintenance BCG immunotherapy. RESULTS: Two hundred patients were included, 155 PI, 21 ReNMI et 24 ReMI. Median follow up was 42 months (1.74-135.9). Mean BCG instillations number was 8 ± 4.2 versus 9.5 ± 4.3 for ReNMI and ReMI respectively (P=0.24). Upstaging (≥ pT2) occurred in 33% of ReNMI. The rate of pN+ was 24%, 42% and 30% for the ReNMI, ReMI et PI respectively (P=0.39). No differences were observed between the groups for lymphovascular invasion, extracapsular extension if pN+, soft tissue surgical margins and adjuvant chemotherapy. 5-year cancer specific survival (CSS) was 48% for the ReNMI, 18% for the ReMI and 47% for the PI (P=0.02). Progression to muscle invasion under BCG therapy was an independent pejorative prognostic factor for CSS (P=0.05). CONCLUSION: BCG failure led to poor prognosis, particularly when tumors progressed to muscle invasion. Recurrent NMI high-grade tumors seemed to have comparable prognosis than PI tumors because of the high amount of upstaging and nodal invasion. BCG failure is a therapeutic emergency.

[Prognostic impact of tumors localized at the prostatic apex]. / Impact pronostique des tumeurs localisées à l'apex prostatique.

OBJECTIVE: The apex is a particular region of the prostate in its surgical dissection and pathological analysis. We sought to evaluate the prognostic value of the apical localization of prostate tumors. METHOD: From 1988 to 2010, data pre- (age, clinical stage, preoperative PSA, biopsy Gleason score) and postoperative (prostate weight, pathologic stage TNM 2010, Gleason score, margin status) of 2765 total prostatectomies were collected prospectively. These data were compared according to existence or absence of tumor at the apex. The prognostic impact of tumor at the apex on biochemical recurrence-free survival (PSA>0.2 ng/mL) has been studied in univariate and multivariate models. RESULTS: One thousand eight hundred seventeen tumors had a location at the apex (65.7%). In univariate analysis, there was a significant difference in the clinical stage, the biopsy and pathological Gleason score, the result of curage, the pathological stage and the margin status between apical tumors and others. With a mean decline of 34.6 months, 502 patients had a biochemical recurrence (18.1%). Disease-free survival at 10 years was 60.7% for tumor at the apex versus 65.9% in other cases. The location at the apex was significantly associated with biochemical recurrence on univariate analysis (P=0.01). After adjustment for clinical and pathological stage, PSA level, Gleason score and surgical margins, the apex was not anymore a pejorative independent predictor (P=0.0087). CONCLUSION: The existence of tumor in the prostatic apex was associated with more aggressive tumoral criteria and was an independent and pejorative predictor of biochemical recurrence-free survival at 10 years in univariate analysis. The apical localization could be an additional argument in the decision of adjuvant therapy after prostatectomy.

[Update on FGFR3 mutation and multiple regional epigenetic silencing (MRES) phenotype in urothelial carcinogenesis]. / Mise au point sur la mutation FGFR3 et le phénotype épigénétique MRES dans la carcinogenèse vésicale.

FGFR3 mutation leads to a constitutive activation of the receptor 3 to Fibroblast Growth Factor. This mutation is early in urothelial carcinogenesis and is strongly associated to low grade papillary tumors. Multiple regional epigenetic silencing (MRES) phenotype corresponds to the transcriptional inactivation of chromosomal regions in muscle invasive bladder cancer, and is strongly associated to the molecular signature of carcinoma in situ. These alterations could be targeted by new specific therapies.

[Pathological findings after radical prostatectomy in men eligible for active surveillance (French trial SURACAP): is the misclassification rate acceptable?]. / Surveillance active du cancer de prostate ayant des critères de latence: les critères SURACAP sont-ils suffisants?

OBJECTIVE: To analyze pathological data of the radical prostatectomy specimen in patients operated for clinically-localized prostate cancer and who meet strict criteria for active surveillance necessary to be included in the French trial SURACAP. PATIENTS AND METHODS: The data of patients who underwent a radical prostatectomy at our institution between 1998 and 2010 were reviewed. We only included the patients that met the usual criteria for active surveillance: clinical stage T1-2a tumor, PSA ≤ 10 ng/mL, biopsy Gleason sum inferior or equal to 6 with no pattern of grade 4 or 5, cancer involvement inferior or equal to two biopsy cores, inferior to 3 mm of malignant tissue in each positive biopsy core. From them, only those who were diagnosed from a second line biopsies cores were included for further analysis. RESULTS: Overall, 48 patient who met the "SURACAP" criteria had a laparoscopic radical prostatectomy at out institution. Mean age was 65.4 years. The mean preoperative PSA was 6.1 ng/mL. Clinical stage of the tumor was T1c in 95% of patients and T2a in 5%. Biopsy Gleason score was 6 (3+3) in 100%. Pathological analysis of the surgical specimen showed that 19% of patients had a seminal vesicle invasion or an extracapsular extension. The Gleason score of the pathological specimen was 6 (3+3) in 57% of patients, 7 (3+4) in 38% and 8 (4+4) in 5% of patients. The Gleason score upgrading was 43% of patients. CONCLUSION: In our experience, 19% of patients who meet the criteria for active surveillance show an extracapsular extension or a seminal vesicle invasion on pathological analysis. Active surveillance is still under evaluation.

[Laparoscopic radical prostatectomy in the elderly (>75 years old): oncological and functional results]. / Prostatectomie radicale laparoscopique chez la personne âgée (>75ans): résultats carcinologiques et fonctionnels.

OBJECTIVE: Prostate cancer incidence increases with age. Radical prostatectomy (RP) seems to be feasible for elderly well-selected patients. We report our experience with patients older than 75 years old who underwent laparoscopic RP. METHODS: From 2000 to 2007, 22 patients older than 75 years old at time of surgery were included in the study. The patient clinical characteristics, the peri- and postoperative data, and the pathological data were collected retrospectively. The overall, specific and PSA-free survival were analysed with Kaplan-Meier method. The functional results such as continence and erectile function were assessed by self-questionnaires. RESULTS: The mean patient age was 75 years (75-81), the median PSA level was 10.77 ng/ml (5-30). The mean American Society of Anesthesiologists score was 2.1 (2-3). Two (9%) perioperative complications occurred but no conversion was necessary. Five patients (23%) had a pT3 disease and the overall positive surgical margins rate was 14%. With a median follow-up of 42 months, no patient has died and five had a biochemical recurrence. At 12-month follow-up, 82% of patients were continent (no pad) and potency (erection sufficient for intercourse) rate was 36% with or without the use of phosphodiesterase-5 inhibitors. CONCLUSION: Laparoscopic RP is feasible for localized prostate cancer in elderly well-selected patients with satisfactory oncological and functional outcomes although the incontinence rate is increased comparing to younger patients.