How to manage renal masses in kidney transplant recipients? A collaborative review by the EAU-YAU kidney transplantation and renal cancer working groups.

INTRODUCTION: Kidney transplant (KT) recipients have a four-times higher risk of renal malignancies compared to general population. As these patients frequently harbor bilateral or multifocal tumors, the management of renal masses is still under debate. OBJECTIVE: To explore the current management of the native kidney masses in KT patients. ACQUISITION OF EVIDENCE: We performed a literature search on MEDLINE/PubMed database. A number of 34 studies were included in the present review. SYNTHESIS OF EVIDENCE: In frail patients with renal masses below 3 cm, active surveillance is a feasible alternative. Nephron-sparing surgery is not justified for masses in the native kidney. Radical nephrectomy is the standard treatment for post-transplant renal tumors of the native kidneys in KT recipients, with laparoscopic techniques leading to significantly less perioperative complication rates as compared to the open approach. Concurrent bilateral native nephrectomy at the time of transplantation can be considered in patients with renal mass and polycystic kidney disease, especially if no residual urinary output is present. Patients with localized disease and successful radical nephrectomy do not require immunosuppression adjustment. In metastatic cases, mTOR agents can ensure efficient antitumoral response, while maintaining proper immunosuppression in order to protect the graft. CONCLUSIONS: Post-transplant renal cancer of the native kidneys is a frequent occurrence. Radical nephrectomy is most frequently performed for localized renal masses. A standardized and widely-approved screening strategy for malignancies of native renal units is yet to be implemented.

Comparison of open and robotic-assisted partial nephrectomy approaches using multicentric data (UroCCR-47 study).

We compared the outcomes of robotic-assisted partial nephrectomy (RPN) and open partial nephrectomy (OPN) using contemporary data to respond to unmet clinical needs. Data from patients included in the registry who underwent partial nephrectomy between January 01, 2014 and June 30, 2017 within 20 centres of the French Network for Research on Kidney Cancer UroCCR were collected (NCT03293563). Statistical methods included adjusted multivariable analyses. Rates of peri- and post-operative transfusion, and of surgical revision, were lower in the RPN (n = 1434) than the OPN (n = 571) group (2.9% vs. 6.0%, p = 0.0012; 3.8% vs. 11.5%, p < 0.0001; 2.4% vs. 6.7%, p < 0.0001, respectively). In multivariable analyses, RPN was independently associated with fewer early post-operative complications than OPN (overall: odds-ratio [95% confidence interval, CI] = 0.48 [0.35-0.66]; severe: 0.29 [0.16-0.54], p < 0.0001 for both) and shorter hospital stays (34% [30%; 37%], p < 0.0001). RPN was also a significantly associated with a decresedrisk of post-operative acute renal failure, and new-onset chronic kidney disease at 3 and 12 months post-surgery. There were no between-group differences in oncological outcomes. In comparison with OPN, RPN was associated with improved peri- and post-operative morbidity, better functional outcomes, and shorter hospital stays. Our results support the use of RPN, even for large and complex tumours.

French AFU Cancer Committee Guidelines - Update 2022-2024: management of kidney cancer.

AIM: To update the recommendations for the management of kidney cancers. METHODS: A systematic review of the literature was conducted from 2015 to 2022. The most relevant articles on the diagnosis, classification, surgical treatment, medical treatment and follow-up of kidney cancer were selected and incorporated into the recommendations. Therefore, the recommendations were updated while specifying the level of evidence (high or low). RESULTS: The gold standard for the diagnosis and evaluation of kidney cancer is contrast-enhanced chest and abdominal CT. MRI and contrast-enhanced ultrasound are indicated in special cases. Percutaneous biopsy is recommended in situations where the results will influence the therapeutic decision. Renal tumours should be classified according to the pTNM 2017 classification, the WHO 2022 classification and the ISUP nucleolar grade. Metastatic kidney cancer should be classified according to the IMDC criteria. Partial nephrectomy is the gold standard treatment for T1a tumours and can be performed by an open approach, by laparoscopy or by robot-guidance. Active surveillance of tumours less than 2cm in size can be considered regardless of the patient's age. Ablative therapies and active surveillance are options in elderly patients with comorbidity. T1b tumours should be treated by partial or radical nephrectomy depending on the complexity of the tumour. Radical nephrectomy is the first-line treatment for locally advanced cancers. Adjuvant treatment with pembrolizumab should be considered in patients at intermediate and high risk for recurrence after nephrectomy. In metastatic patients: Immediate cytoreductive nephrectomy may be offered to oligometastatic patients in combination with local treatment of metastases if this can be complete and delayed cytoreductive nephrectomy can be proposed for patients with a complete response or a significant partial response. Medical treatment should be proposed as first-line therapy for patients with a poor or intermediate prognosis. Surgical or local treatment of metastases can be proposed in case of single or oligo-metastases. The recommended first-line drugs for metastatic patients with clear cell renal carcinoma are the combinations axitinib/pembrolizumab, nivolumab/ipililumab, nivolumab/cabozantinib and lenvatinib/pembrolizumab. Cabozantinib is the recommended first-line treatment for patients with metastatic papillary carcinoma. Cystic tumours should be classified according to the Bosniak classification. Surgical removal should be proposed as a priority for Bosniak III and IV lesions. It is recommended that patient monitoring be adapted to the aggressiveness of the tumour. CONCLUSION: These updated recommendations are a reference that will allow French and French-speaking practitioners to improve kidney cancer management.

[High risk localized and locally advanced prostate cancer: Long-term oncological outcomes after prostatectomy]. / Cancer de la prostate localisé de haut risque et localement avancé : résultats oncologiques à long terme de la prostatectomie.

INTRODUCTION: High risk localized and locally advanced forms are responsible for the vast majority of specific deaths from prostate cancer among non-metastatic diseases at diagnosis. No randomized study has yet been published to establish the best local treatment in terms of survival. AIM: Conduct a large-volume cohort study with long-term follow-up to analyze specific and overall survival outcomes after surgery. METHOD: A single-center retrospective study of all patients operated on for localized high-risk and locally advanced prostate cancer was performed. Actuarial survival analyses and multivariate analyses were performed to discern predictive risk factors. RESULTS: Five hundred patients were included. MRI stage was≥iT3a in 40.7% of cases and 50.2% of patients had a Gleason score≥8 on biopsy. The mean follow-up was 63.1 months. The overall, specific and biological recurrence-free survival were respectively 77.6%, 93.9% and 26.8% at 10 years. A PSA level≥20, a Gleason score on biopsy≥9 and a MRI stage≥iT3a were significantly associated with the 10-years biological recurrence risk. CONCLUSION: This study shows very good long-term oncological results. In the absence of a randomized controlled trial, these results suggest the primary role of surgery in this indication and support the evolution of current practices. We pointed out very pejorative features that might help selection of the best candidates for surgical treatment.

Robotic-assisted laparoscopy living donor nephrectomy: Technique and results of a monocentric retrospective series.

INTRODUCTION: Robot-assisted nephrectomy for living kidney donation (LKD) has been described in the literature as a safe and reproducible technique in high volume centers with extensive robotic surgery experience. Any surgical procedure in a healthy individual ought to be safe in regards to complications. The objective of this study was to evaluate the Robotic-assisted Living Donor Nephrectomy (RLDN) experience in a robotic surgery expert center. METHODS: This is a retrospective study from 11/2011 and 12/2019. In total, 118 consecutive Living Donor (LD) kidney transplants were performed at our institution. All the procedures were performed by robotic-assisted laparoscopic approach. Extraction was performed by iliac (IE), vaginal (VE) or umbilical extraction (UE). The left kidney was preferred even if the vascular anatomy was not modal. RESULTS: For donors: the median operative time was 120min with 50mL of blood loss. The median warm ischemia time was 4min, with a non-significant shorter duration with the UE (4min) in comparison with IE or VE (5min). Nine patients had postoperative complications including 1 grade II (blood transfusion) and 1 grade IIIb (vaginal bleeding after VE). None of our procedures were converted to open surgeries and no deaths were reported. For the recipients: 1.7% presented delayed graft function; their median GFR at 1 year was 61mL/min/1.73m2. CONCLUSION: RLDN in an expert center appears to be a safe technique. The advantages of the robot device in terms of ergonomy don't hamper the surgical outcomes. Donor, recipient and graft survivals seem comparable to the reported laparoscopic outcomes in the literature.

[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.

[Indocyanine green fluorescence to visualize the ureteric vascularization of kidney transplants: An exploratory study]. / Visualiser la vascularisation urétérale des transplants rénaux par fluorescence au vert d'indocyanine : étude exploratoire.

INTRODUCTION: Urinary complications after kidney transplantation are common and can compromise renal function. While they are mainly attributed to ischemic lesions of the ureter, there is no existing method to evaluate its vascularization during surgery. The aim of the study was to evaluate if indocyanine green, revealed by infra-red light andused to visualize tissue perfusion, could provide an appreciation of the ureter's vascularization during kidney transplantation. METHODS: This feasibility study was conducted over one month, on eleven consecutive kidney transplants. During transplantation, an injection of indocyanine green enabled the surgeon to visualize in real time with an infra-red camera the ureter fluorescence. Its intensity was reported on a qualitative and semi-quantitative scale. Occurrence of urinary complications such as stenosis or ureteral fistula were collected during 6 months. RESULTS: In all of the 11 cases (100%), the last centimeters of the ureters were not fluorescent. Three (27%) ureters were poorly or partiallly fluorescent. Out of these three cases, only one case of urinary fistula occurred, followed by ureteric stenosis. In the series, two fistulas (18%) and two ureteric stenoses (18%) occurred. No side effects were observed. The low number of events did not allow statistical analysis. CONCLUSION: Infra-red fluorescence of indocyanine green could be a simple and innovative way to appreciate the transplant's ureteric vascularization during kidney transplantation. It could help surgeons to identify the level of ureter section and to decide the anastomosis technique, in order to limit urinary complications. LEVEL OF EVIDENCE: 3.

[Evaluation and results of ablative therapies in prostate cancer]. / Modalités d'évaluation et résultats des traitements ablatifs dans le cancer de la prostate.

OBJECTIVE: To perform a state of the art about methods of evaluation and present results in ablative therapies for localized prostate cancer. METHODS: A review of the scientific literature was performed in Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of keywords. Publications obtained were selected based on methodology, language and relevance. After selection, 102 articles were analysed. RESULTS: Analyse the results of ablative therapies is presently difficult considering the heterogeneity of indications, techniques and follow-up. However, results from the most recent and homogeneous studies are encouraging. Oncologically, postoperative biopsies (the most important criteria) are negative (without any tumor cells in the treated area) in 75 to 95%. Functionally, urinary and sexual pre-operative status is spared (or recovered early) in more than 90% of the patients treated. More and more studies underline also the correlation between the results and the technique used considering the volume of the gland and, moreover, the "index lesion" localization. CONCLUSION: The post-treatment pathological evaluation by biopsies (targeted with MRI or, perhaps in a near future, with innovative ultrasonography) is the corner stone of oncological evaluation of ablative therapies. Ongoing trials will allow to standardize the follow-up and determine the best indication and the best techniques in order to optimize oncological and functional results for each patient treated.

Vimentin over-expression and carbonic anhydrase IX under-expression are independent predictors of recurrence, specific and overall survival in non-metastatic clear-cell renal carcinoma: a validation study.

PURPOSE: Clinical outcomes prognostic markers are awaited in clear-cell renal carcinoma (ccRCC) to improve patient-tailored management and to assess six different markers' influence on clinical outcomes from ccRCC specimen and their incremental value combined with TNM staging. MATERIALS AND METHODS: This is a retrospective, multicenter study. One hundred and forty-three patients with pT1b-pT3N0M0 ccRCC were included. Pathology specimens from surgeries were centrally reviewed, mounted on a tissue micro-array and stained with six markers: CAIX, c-MYC, Ki67, p53, vimentin and PTEN. Images were captured through an Ultra Fast Scanner. Tumor expression was measured with Image Pro Plus. Cytoplasmic markers (PTEN, CAIX, vimentin, c-MYC) were expressed as surface percentage of expression. Nuclear markers (Ki67, p53) were expressed as number of cells/mm2. Clinical data and markers expression were compared with clinical outcomes. Each variable was included in the Cox proportional multivariate analyses if p < 0.10 on univariate analyses. Discrimination of the new marker was calculated with Harrell's concordance index. RESULTS: At median follow-up of 63 months (IQR 35.0-91.8), on multivariate analysis, CAIX under-expression and vimentin over-expression were associated with worse survival (recurrence, specific and overall survival). A categorical marker CAIX-/Vimentin+ with cutoff points for CAIX and vimentin of 30 and 50 %, respectively, was designed. The new CAIX-/Vimentin+ marker presented a good concordance and comparable calibration to the reference model. Limitations are the retrospective design, the need for external validation and the large study period. CONCLUSION: Using an automated technique of measurement, CAIX and vimentin are independent predictors of clinical outcomes in ccRCC.

Characteristics and prognosis of pneumococcal endocarditis: a case-control study.

Case series have suggested that pneumococcal endocarditis is a rare disease, mostly reported in patients with co-morbidities but no underlying valve disease, with a rapid progression to heart failure, and high mortality. We performed a case-control study of 28 patients with pneumococcal endocarditis (cases), and 56 patients with non-pneumococcal endocarditis (controls), not matched for sex and age, during the years 1991-2013, in one referral centre. Alcoholism (39.3% versus 10.7%; p <0.01), smoking (60.7% versus 21.4%; p <0.01), the absence of previously known valve disease (82.1% versus 60.7%; p 0.047), heart failure (64.3% versus 23.2%; p <0.01) and shock (53.6% versus 23.2%; p <0.01) were more common in pneumococcal than in non-pneumococcal endocarditis. Cardiac surgery was required in 64.3% of patients with pneumococcal endocarditis, much earlier than in patients with non-pneumococcal endocarditis (mean time from symptom onset, 14.1 ± 18.2 versus 69.0 ± 61.1 days). In-hospital mortality rates were similar (7.1% versus 12.5%). Streptococcus pneumoniae causes rapidly progressive endocarditis requiring life-saving early cardiac surgery in most cases.