PIRADS≥4 MRI lesion: Is performing systematic biopsies still essential for detecting clinically significant prostate cancer?

INTRODUCTION: In the era of targeted prostate biopsies, the necessity of performing randomized biopsies systematically is under question. Our objective is to evaluate the rate of clinically significant prostate cancer (csPCa), defined by presence of ISUP≥2 prostate cancer, diagnosed only on randomized cores in case of a PIRADS≥4 target lesion on MRI. The secondary objective is to evaluate whether specific variables can predict the presence of undetected csPCa in targeted biopsies. METHODS: Retrospective data on targeted biopsies performed from 2015 to 2021 in our hospital were collected. Procedures were performed with MRI/Transrectal US fusion Trinity platform from Koelis®. All the MRI images were reviewed and the targets were classified using the PIRADS V2.1 classification. Inclusion criteria comprised procedures featuring at least one PIRADS≥4 targeted lesion were included. All procedures consisted 1-4 targeted cores and 12-core systematic biopsy. RESULTS: We included 358 patients. In 44 patients (12.3%) csPCa was exclusively detected in randomized cores. Among these cases, only 12 patients (27.2%) showed no cancer on the targeted biopsies. Merely 4 patients (9.09%) lacked csPCa-positive cores on the same side as the index lesion. Factors such as PSA, PSA density, prostate volume, and digital rectal examination showed no significant association with the presence of csPCa exclusively on randomized cores. Likewise, the size, location, and PIRADS classification of the target demonstrated no significant impact. CONCLUSION: Our findings indicate that in 12.3% of cases, targeted biopsies alone are insufficient for detecting the presence of csPCa. As such, systematic biopsies remain necessary to date.

To what extent does freezing impact the mid-infrared signature of urine? Case of patients attending urology department.

Urine is a very interesting and attractive biofluid for biomarker discovery and medical diagnosis research due to its non-invasiveness collection and richness of potential biomarkers. Fourier-Transform Infrared (FTIR) spectroscopy applied on urine samples is a promising tool that could be used as a screening method for various diseases. However, during method development, frozen urine is more accessible, especially for inter-laboratory studies, whereas in routine application fresh urine is more convenient. Here, the objective of our work is to evaluate the freezing impact on mid-infrared signature of urine samples. Therefore, both fresh and frozen urine samples from twenty patients were analysed in a dried form. These samples were collected from patients consulting for cystoscopy examination. Simultaneously, centrifugation was also conducted on 10 of all included patients. Principal component analysis (PCA) revealed that patient inter-variabilities are higher than variability due to the freezing step. Then, Euclidean distance between fresh and frozen urine of each patient highlighted that the impact of freezing is different from one patient to another. Adding the centrifugation step slightly minimized intra-patient variability compared to not centrifugated samples. This study contributes to define experimental conditions for urine analysis development for translational application in biomedical field.

Surgeon seniority and experience have no effect on CaP detection rates using MRI/TRUS fusion-guided targeted biopsies.

OBJECTIVE: To determine (i) whether urologist seniority and experience are associated with prostate cancer (CaP) and clinically significant CaP (csCaP) detection rates using magnetic resonance imaging/ultrasound (MRI/US) fusion-guided targeted biopsies, taking multiparametric magnetic resonance imaging (mpMRI) as the reference standard, and (ii) if cancer detection rates (CDR) differ across regions of the prostate using Dickinson's 27-sector map, regardless of seniority. METHODS: We retrospectively reviewed a consecutive series of patients with suspicion of prostate cancer who underwent targeted and systematic biopsies at 1 center by 1 of 7 urologists (2 seniors and 5 juniors) between January 1, 2016 and December 31, 2021, following positive mpMRI. RESULTS: The cohort comprised 403 patients (454 lesions) aged 67.7±6.8. The combined (junior and senior) CDR was 57% for CaP and 28% for csCaP. There were no differences in CDR between junior and senior urologists for CaP (58% vs. 55%, P = 0.538) or csCaP (29% vs. 26%, P = 0.58). A general trend was observed for the learning curve, which indicated increasing CDR with urologist experience. Across the 27 sectors, combined CDR ranged between 39% and 99% for CaP and 1% to 67% for csCaP. When grouping anterior vs. posterior sectors, there were no differences in combined CDR of CaP (64% vs. 67%, P = 0.48) and csCaP (31% vs. 38%, P = 0.19) CONCLUSIONS: Urologist seniority is not associated with CDR, urologist experience tends to improve cancer detection, and CDR does not differ between the anterior and posterior regions of the prostate.

Prognostic value of programmed death ligand-1 and programmed death-1 expression in patients with upper tract urothelial carcinoma.

OBJECTIVE: To evaluate the prognostic value of programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) expression in patients with upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: A retrospective multicentre study was conducted in 283 patients with UTUC treated with radical nephroureterectomy (RNU) between 2000 and 2015 at 10 French hospitals. Immunohistochemistry analyses were performed using 2 mm-core tissue microarrays with NAT105® and 28.8® antibodies at a 5% cut-off for positivity on tumour cells and tumour-infiltrating lymphocytes to evaluate PD-L1 and PD-1 expression, respectively. Multivariable Cox regression models were used to determine the independent predictors of recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). RESULTS: Overall, 63 (22.3%) and 220 (77.7%) patients with UTUC had PD-L1-positive and -negative disease, respectively, while 91 (32.2%) and 192 (67.8%) had PD-1-positive and -negative disease, respectively. Patients who expressed PD-L1 or PD-1 were more likely to have pathological tumour stage ≥pT2 (68.3% vs 49.5%, P = 0.009; and 69.2% vs 46.4%, P < 0.001, respectively) and high-grade (90.5% vs 70.0%, P = 0.001; and 91.2% vs 66.7%, P < 0.001, respectively) disease with lymphovascular invasion (52.4% vs 17.3%, P < 0.001; and 39.6% vs 18.2%, P < 0.001, respectively) as compared to those who did not. In multivariable Cox regression analysis adjusting for each other, PD-L1 and PD-1 expression were significantly associated with decreased RFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.09-3.08, P = 0.023; and HR 1.59, 95% CI 1.01-2.54, P = 0.049; respectively), CSS (HR 2.73, 95% CI 1.48-5.04, P = 0.001; and HR 1.96, 95% CI 1.12-3.45, P = 0.019; respectively) and OS (HR 2.08, 95% CI 1.23-3.53, P = 0.006; and HR 1.71, 95% CI 1.05-2.78, P = 0.031; respectively). In addition, multivariable Cox regression analyses evaluating the four-tier combination of PD-L1 and PD-1 expression showed that only PD-L1/PD-1-positive patients (n = 38 [13.4%]) had significantly decreased RFS (HR 3.07, 95% CI 1.70-5.52; P < 0.001), CSS (HR 5.23, 95% CI 2.62-10.43; P < 0.001) and OS (HR 3.82, 95% CI 2.13-6.85; P < 0.001) as compared to those with PD-L1/PD-1-negative disease (n = 167 [59.0%]). CONCLUSIONS: We observed that PD-L1 and PD-1 expression were both associated with adverse pathological features that translated into an independent and cumulative adverse prognostic value in UTUC patients treated with RNU.

Cost-effectiveness of robotic-assisted surgery vs open surgery in the context of partial nephrectomy for small kidney tumors.

To evaluate the cost-effectiveness of robotic-assisted surgery compared to open surgery in the context of partial nephrectomy for small kidney tumor management. This is a retrospective study using data from 395 patients operated on by either robot-assisted surgery (RAPN) or by open partial nephrectomy (OPN); one hospital performed RAPN exclusively and the second hospital, OPN exclusively. Cost-effectiveness analysis was conducted from the perspective of the National Health Insurance System (NHIS) by considering the costs of the initial hospital stay and the cost of complications. Clinical outcome was defined by the avoidance of major complications during the 12 months postoperatively. Major complications were absent in 82% of patients in the OPN group and 93% of patients in the RAPN group, with 11% in favor of robotic assistance (p < 0.001). The average cost per patient, including the costs of complications, were, respectively, 9637 € and 8305 € for the OPN and RAPN groups. Robotic assistance was associated with a 1332 € lower cost (p < 0.001). The incremental cost-effectiveness ratio (ICER) is estimated at - 12,039 €. From the perspective of the public payer, robotic assistance was associated with a lower rate of postoperative complications and a lower average cost per patient. Robotic-assisted surgery was an efficient alternative to open surgery in partial nephrectomy. Trial registration number: NCT05089006 (October 22, 2021).

Machine-learning approach for prediction of pT3a upstaging and outcomes of localized renal cell carcinoma (UroCCR-15).

OBJECTIVES: To assess the impact of pathological upstaging from clinically localized to locally advanced pT3a on survival in patients with renal cell carcinoma (RCC), as well as the oncological safety of various surgical approaches in this setting, and to develop a machine-learning-based, contemporary, clinically relevant model for individual preoperative prediction of pT3a upstaging. MATERIALS AND METHODS: Clinical data from patients treated with either partial nephrectomy (PN) or radical nephrectomy (RN) for cT1/cT2a RCC from 2000 to 2019, included in the French multi-institutional kidney cancer database UroCCR, were retrospectively analysed. Seven machine-learning algorithms were applied to the cohort after a training/testing split to develop a predictive model for upstaging to pT3a. Survival curves for disease-free survival (DFS) and overall survival (OS) rates were compared between PN and RN after G-computation for pT3a tumours. RESULTS: A total of 4395 patients were included, among whom 667 patients (15%, 337 PN and 330 RN) had a pT3a-upstaged RCC. The UroCCR-15 predictive model presented an area under the receiver-operating characteristic curve of 0.77. Survival analysis after adjustment for confounders showed no difference in DFS or OS for PN vs RN in pT3a tumours (DFS: hazard ratio [HR] 1.08, P = 0.7; OS: HR 1.03, P > 0.9). CONCLUSIONS: Our study shows that machine-learning technology can play a useful role in the evaluation and prognosis of upstaged RCC. In the context of incidental upstaging, PN does not compromise oncological outcomes, even for large tumour sizes.

Clinical and oncological outcomes of open partial nephrectomy versus robot assisted partial nephrectomy over 15 years.

Partial nephrectomy (PN) is the gold standard surgical treatment for localized kidney cancer. The objective of our study was to compare clinical and perioperative outcomes of open partial nephrectomy (OPN) and robotic-assisted partial nephrectomy (RAPN). We retrospectively collected all patients who underwent PN for kidney cancer between 2007 and 2019 at two French academic urology departments. Clinical and perioperative outcomes and complications were compared between the OPN group and the RAPN group. Recurrence-free survival (RFS) and overall survival (OS) were compared using the log-rank test. We included 405 patients. The maximum follow-up time was 13.6 years in the OPN group and 7.1 years in the RAPN group. The OPN group was associated with more blood loss and longer hospital stay (respectively, 287 ml vs. 62.1 ml; p < 0.001 and 8.54 days vs. 4.96 days; p < 0.001). Ischemia time was shorter in the OPN group (11.4 min vs. 16.9 min; p < 0.001). The rate of complications during hospitalization and after discharge from hospital was higher in the OPN group (respectively, n = 51 vs. 30; p = 0.031 and n = 31 vs. 14; p < 0.001). RFS and OS were similar in both groups. In our study, RAPN has better perioperative outcomes with shorter hospital stay and less blood loss but also fewer early and late complications. However, we did not find any difference in terms of RFS and OS.

Presence of a Novel Anatomical Structure May Cause Bleeding When Using the Calyx Access in Mini-Percutaneous Nephrolithotomy.

Background: Fused renal pyramid (FRP) is a kidney anatomical structure which was first identified by us. The vascular anatomy of FRP exhibits different from that of the normal renal pyramid (NRP), manifested by the distribution of the ectopic interlobar arteries in FRP. In this study, we analyzed the effect of FRPs on bleeding when using calyx access in mini-percutaneous nephrolithotomy (PCNL). Patients and Methods: Overall, 633 patients who underwent ultrasound-guided single-tract mini-PCNL were divided into two groups according to the puncture method used: in group A, puncture was performed through the axial direction of the renal calyx, the line from the apex of the fornix to the center of the neck plane under B-mode ultrasound guidance; and in group B, Doppler ultrasound-guided axillary puncture through calyces corresponding to NRPs when the plane of renal column blood vessels on both sides was selected or calyx puncture through the hypovascular area of the FRPs. Relevant demographic and clinical data were retrospectively analyzed. Results: The two groups exhibited similar baseline characteristics. No significant differences were found in hemoglobin reduction, puncture site, tract size, postoperative creatinine level, or stone-free rate between the two groups (P > 0.05). Blood transfusion and embolization rates in group B were significantly lower than those in group A (P = 0.03 and 0.045, respectively). No differences were found between the two groups in terms of persistent pain, hydrothorax, fever, subcapsular hematoma, and urosepsis (P > 0.05). The overall complication rate was not significantly different between the two groups (P = 0.505). Conclusions: FRP is a non-negligible anatomical structure that may cause hemorrhage when using calyx access. Doppler ultrasound can identify ectopic blood vessels in FRPs to reduce bleeding during calyx access in mini-PCNL procedures.

Association of patients' sex with treatment outcomes after intravesical bacillus Calmette-Guérin immunotherapy for T1G3/HG bladder cancer.

PURPOSE: To investigate the association of patients' sex with recurrence and disease progression in patients treated with intravesical bacillus Calmette-Guérin (BCG) for T1G3/HG urinary bladder cancer (UBC). MATERIALS AND METHODS: We analyzed the data of 2635 patients treated with adjuvant intravesical BCG for T1 UBC between 1984 and 2019. We accounted for missing data using multiple imputations and adjusted for covariate imbalance between males and females using inverse probability weighting (IPW). Crude and IPW-adjusted Cox regression analyses were used to estimate the hazard ratios (HR) with their 95% confidence intervals (CI) for the association of patients' sex with HG-recurrence and disease progression. RESULTS: A total of 2170 (82%) males and 465 (18%) females were available for analysis. Overall, 1090 (50%) males and 244 (52%) females experienced recurrence, and 391 (18%) males and 104 (22%) females experienced disease progression. On IPW-adjusted Cox regression analyses, female sex was associated with disease progression (HR 1.25, 95%CI 1.01-1.56, p = 0.04) but not with recurrence (HR 1.06, 95%CI 0.92-1.22, p = 0.41). A total of 1056 patients were treated with adequate BCG. In these patients, on IPW-adjusted Cox regression analyses, patients' sex was not associated with recurrence (HR 0.99, 95%CI 0.80-1.24, p = 0.96), HG-recurrence (HR 1.00, 95%CI 0.78-1.29, p = 0.99) or disease progression (HR 1.12, 95%CI 0.78-1.60, p = 0.55). CONCLUSION: Our analysis generates the hypothesis of a differential response to BCG between males and females if not adequately treated. Further studies should focus on sex-based differences in innate and adaptive immune system and their association with BCG response.

Identification of Neoadjuvant Chemotherapy Response in Muscle-Invasive Bladder Cancer by Fourier-Transform Infrared Micro-Imaging.

BACKGROUND: Neoadjuvant chemotherapy (NAC) improves survival in responder patients. However, for non-responders, the treatment represents an ineffective exposure to chemotherapy and its potential adverse events. Predicting the response to treatment is a major issue in the therapeutic management of patients, particularly for patients with muscle-invasive bladder cancer. METHODS: Tissue samples of trans-urethral resection of bladder tumor collected at the diagnosis time, were analyzed by mid-infrared imaging. A sequence of spectral data processing was implemented for automatic recognition of informative pixels and scoring each pixel according to a continuous scale (from 0 to 10) associated with the response to NAC. The ground truth status of the responder or non-responder was based on histopathological examination of the samples. RESULTS: Although the TMA spots of tumors appeared histologically homogeneous, the infrared approach highlighted spectral heterogeneity. Both the quantification of this heterogeneity and the scoring of the NAC response at the pixel level were used to construct sensitivity and specificity maps from which decision criteria can be extracted to classify cancerous samples. CONCLUSIONS: This proof-of-concept appears as the first to evaluate the potential of the mid-infrared approach for the prediction of response to neoadjuvant chemotherapy in MIBC tissues.

PD-L1 expression and pattern of immune cells in pre-treatment specimens are associated with disease-free survival for HR-NMIBC undergoing BCG treatment.

PURPOSE: To assess the association between PD-L1 expression and disease-free survival (DFS) in High-Risk Non-Muscle Invasive Bladder Cancer (HR-NMIBC) patients treated with intravesical Bacillus Calmette-Guerin (BCG) instillations (IBI). METHODS: Retrospective study in five French centres between 2001 and 2015. Participants were 140 patients with histologically confirmed HR-NMIBC. All patients received induction and maintenance IBI. Pathological stage/grade, concomitant carcinoma in situ, lesion number and tumour size were recorded. CD3, CD8 and PD-L1 expression in tumour cells and in T cells in the tumour microenvironment (TME) was determined immunohistochemically. Median follow-up was 54.2 months. The primary outcome measure was DFS. Univariable and multivariable analyses were performed using the log rank test and Cox proportional hazards model. RESULTS: Of the 140 NMIBC, 52 (37.1%) were Ta, 88 (62.9%) were T1 and 100% were high grade. Median number of maintenance IBI was six (range 1-30). Twenty-five (17.9%) patients had recurrence/progression. In multivariable analysis, age (HR 1.07 [95% CI 1.02-1.13], p = 0.009), PD-L1 expression in tumour cells (HR per 10 units = 1.96 [95% CI 1.28-3.00], p = 0.02) and CD3/CD8 ratio (HR per 10 units = 3.38 [95% CI 1.61-7.11], p = 0.01) were significantly associated with DFS. However, using the cut-off corresponding for each PD-L1 antibodies, PD-L1 + status was not associated with DFS. CONCLUSION: Despite an association between PD-L1 expression and BCG failure in HR-NMIBC, the PD-L1 + status was not a prognostic factor in the response of BCG. Moreover, we confirmed the key role played by the IC within the microenvironment in BCG treatment. These findings highlighted the rationale to combine BCG and PD-L1/PD-1 antibodies in early bladder cancer.

Intra-abdominal hypertension in early post-kidney transplantation period is associated with impaired graft function.

BACKGROUND: Moderate hyperhydration is often achieved in the early post-kidney transplantation period. Whether this strategy could lead to the development of intra-abdominal hypertension (IAH) has never been assessed so far. We aimed to study the incidence of IAH after kidney transplantation and its association with graft function recovery. METHODS: We conducted a prospective monocentric study among patients undergoing kidney transplantation at the University Hospital of Reims between May 2017 and April 2019. Intravesical pressure (IVP) was monitored every 8 h from Day 0 to 3. RESULTS: A total of 107 patients were enrolled. Among 55 patients included in the analysis, 74.5% developed IAH. Body mass index >25 kg/m2 was associated with IAH development {odds ratio [OR] 10.4 [95% confidence interval (CI) 2.0-52.9]; P = 0.005}. A previous history of peritoneal dialysis was protective [OR 0.06 (95% CI 0.01-0.3); P = 0.001]. IAH Grades III and IV occurred in 30.9% of patients and correlated with higher Day 3 creatininaemia (419.6 ± 258.5 versus 232.5 ± 189.4 µmol/L; P = 0.02), higher delayed graft function incidence (41.2 versus 7.9%; P = 0.04), lower Kirchner index measured using scintigraphy (0.47 ± 0.09 versus 0.64 ± 0.09; P = 0.0005) and decreased Day 30 estimated glomerular filtration rate (35.8 ± 18.8 versus 52.5 ± 21.3, P = 0.05). IAH patients had higher fluid balance (P = 0.02). Evolution of IVP correlated with weight gain (P < 0.01) and central venous pressure (P < 0.001). CONCLUSIONS: IAH is frequent after kidney transplantation and IAH Grades III and IV are independently associated with impaired graft function. These results question current haemodynamic objectives and raise for the first time interest in intra-abdominal pressure monitoring in these patients. CLINICAL TRIAL NOTATION: ClinicalTrials.gov identifier: NCT03478176.

The Anatomic Structure of a Fused Renal Pyramid and Its Clinical Significance in the Establishment of Percutaneous Renal Access.

OBJECTIVE: To explore the clinical significance of the fused renal pyramid (FRP) in establishing percutaneous renal access, and the anatomic basis for avoiding vascular injury caused by puncturing through this renal pyramid with the aim of achieving accurate puncture in percutaneous nephrolithotomy. MATERIALS AND METHODS: Sixty-two cadaveric kidneys and 105 porcine kidneys were selected for the assessment of regional anatomy, to explore the anatomic structure of the FRP and determine its frequency. Then, we compared the effects of 4 different puncture paths on the occurrence of renal vascular injury when respectively punctured through the normal renal pyramid (group A), the centerline of one side pyramid of the FRP (group B), the center of the entire FRP (group C) and the renal column (group D). RESULTS: The incidence of FRP in human kidneys is not low. The artery in the kidney can be divided into 6 grades. The grade IV branch-interlobar artery courses through the FRP. There was significant difference in the degree of arterial injury between the group A and C (P = .003), while no significant difference between the group A and B (P = .151). There was significant difference in the proportion of interlolar artery injury between group A and C (P <.001), while no significant difference between group A and B (P = .239). CONCLUSION: It is necessary to carefully identify and bypass the FRP when establishing a percutaneous renal access. If unavoidable, the puncture path should be on the centerline of one side pyramid of the FRP.

Efficacy and safety of artificial urinary sphincter (AUS): Results of a large multi-institutional cohort of patients with mid-term follow-up.

AIMS: To assess efficacy and safety as well as predictive factors of dry rate and freedom from surgical revision in patients underwent AUS placement. The artificial urinary sphincter (AUS) is still considered the standard for the treatment of moderate to severe post-prostatectomy stress urinary incontinence (SUI). However, data reporting efficacy and safety from large series are lacking. METHODS: A multicenter, retrospective study was conducted in 16 centers in Europe and USA. Only primary cases of AUS implantation in non-neurogenic SUI after prostate surgery, with a follow-up of at least 1 year were included. Efficacy data (continence rate, based on pad usage) and safety data (revision rate in case of infection and erosion, as well as atrophy or mechanical failure) were collected. Multivariable analyses were performed in order to investigate possible predictors of the aforementioned outcomes. RESULTS: Eight hundred ninety-two men had primary AUS implantation. At 32 months mean follow-up overall dry rate and surgical revision were 58% and 30.7%, respectively. Logistic regression analysis showed that patients without previous incontinence surgery had a higher probability to be dry after AUS implantation (OR: 0.51, P = 0.03). Moreover institutional case-load was positively associated with dry rate (OR: 1.18; P = 0.005) and freedom from revision (OR: 1.51; P = 0.00). CONCLUSIONS: The results of this study showed that AUS is an effective option for the treatment of SUI after prostate surgery. Moreover previous incontinence surgery and low institutional case-load are negatively associated to efficacy and safety outcomes.

Quantum dot-based fluorescent probes for targeted imaging of the EJ human bladder urothelial cancer cell line.

QDs are a type of inorganic nanoparticle with unique optical properties. As a fluorescent label, QDs are widely used in biomedical fields. In the present study, fluorescent probes of quantum dots (QDs) conjugated with a prostate stem cell antigen (PSCA) monoclonal antibody (QD-PSCA) were prepared to study the targeted imaging of QD-PSCA probes in EJ human bladder urothelial cancer cells and analyze the feasibility of QD-based non-invasive tumor-targeted imaging in vivo. QDs with an emission wavelength of 605 nm (QD605) were conjugated with PSCA to prepare QD605-PSCA fluorescent probes by chemical covalent coupling. The optical properties of the probes coupled and uncoupled with PSCA were measured and assessed using an ultraviolet spectrophotometer and a fluorescence spectrophotometer. Direct immune-fluorescent labeling was utilized to detect and analyze imaging of the probes for EJ cells. The results revealed that QD605-PSCA probes retained the fluorescent properties of QD605 and the immunogenicity of the PSCA protein. The probes were able to specifically recognize the PSCA protein expressed in bladder cancer cells, while fluorescence was stable and had a long duration. The present study suggests that QD-PSCA fluorescent probes may be useful for specific targeted labeling and imaging in bladder urothelial cancer cells. Furthermore, the probes possess good optical stability and may be useful for research into non-invasive targeted imaging, early diagnosis and targeted in vivo tumor therapy.

Diagnosis and treatment of inguinal hernia of the bladder: a systematic review of the past 10 years.

OBJECTIVE: Inguinoscrotal hernia (ISH) of the bladder is a rare condition involved in less than 4% of inguinal hernias. In most cases, it occurs to men older than 50 years who are overweight. Little is known about the subject and mainly based on case reports. When undiagnosed, it may be associated with bladder injuries during hernia repair. There is also no consensus on the ideal repair technique to use. The aim of the study is to evaluate the particularity of the management of the inguinal herniation of the bladder in term of diagnosis, choice and results of treatments. METHODS: A Prisma systematic review of the literature was performed over the last 10 years using a database. We selected 51 articles including 64 patients with ISH of the bladder. RESULTS: ISH of the bladder mainly occurred in overweight men aged over 50 years (Body Mass Index >30). Symptoms were reported for 76% of the patients (n=49), including inguinal swelling 60% of cases (n=38), lower urinary tract symptoms (48%), pain (40%) and a reduction of an inguinal mass after voiding (12.7%). Diagnosis was incidental on imaging for 7 patients, during inguinal repair surgery for 8, or on imaging performed following symptoms for the remaining 49 patients. Surgical repair was reported for 46 patients (71%) including various procedures as open surgery (80%) and laparoscopic approaches (20%). Excellent short term results were reported. CONCLUSION: ISH of the bladder seams more likely to occur with patients suffering from lower urinary tract obstruction and best diagnosed with a computerized tomography scan. Various surgical techniques are reported.

Risk factors for loco-regional recurrence after radical cystectomy of muscle-invasive bladder cancer: A systematic-review and framework for adjuvant radiotherapy.

BACKGROUND: Radical cystectomy (RC) associated with pelvic lymph node dissection (PLND) is the most common local therapy in the management of non-metastatic muscle invasive bladder cancer (MIBC). Loco-regional recurrence (LRR), however, remains a common and important therapeutic challenge associated with poor oncologic outcomes. We aimed to systematically review evidence regarding factors associated with LRR and to propose a framework for adjuvant radiotherapy (RT) in patients with MIBC. METHODS: We performed this systematic review in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. We searched the PubMed database for articles related to MIBC and associated treatments, published between January 1980 and June 2015. Articles identified by searching references from candidate articles were also included. We retrieved 1383 publications from PubMed and 34 from other sources. After an initial screening, a review of titles and abstracts, and a final comprehensive full text analysis of papers assessed for eligibility, a final consensus on 32 studies was obtained. RESULTS: LRR is associated with specific patient-, tumor-, center- or treatment-related variables. LRR varies widely, occurring in as many as 43% of the cases and is strongly related to survival outcomes. While perioperative treatment does not impact on LRR, pathological factors such as pT, pN, positive margins status, extent of PLND, number of lymph nodes removed and/or invaded are correlated with LRR. Patients with pT3-T4a and/or positive lymph-nodes and/or limited pelvic lymph-node dissection and/or positive surgical margins have been distributed in LRR risk groups with accuracy. CONCLUSIONS: LRR patterns are well-known and for selected patients, adjuvant treatments could target this event. Intrinsic tumor subtype may guide future criteria to define a personalized treatment strategy. Prospective trials evaluating safety and efficacy of adjuvant RT are ongoing in several countries.

Development of immunotherapy in bladder cancer: present and future on targeting PD(L)1 and CTLA-4 pathways.

PURPOSE: Over the past 3 decades, no major treatment breakthrough has been reported for advanced bladder cancer. Recent Food and Drug Administration (FDA) approval of five immune checkpoint inhibitors in the management of advanced bladder cancer represent new therapeutic opportunities. This review examines the available data of the clinical trials leading to the approval of ICIs in the management of metastatic bladder cancer and the ongoing trials in advanced and localized settings. METHODS: A literature search was performed on PubMed and ClinicalTrials.gov combining the MeSH terms: 'urothelial carcinoma' OR 'bladder cancer', and 'immunotherapy' OR 'CTLA-4' OR 'PD-1' OR 'PD-L1' OR 'atezolizumab' OR 'nivolumab' OR 'ipilimumab' OR 'pembrolizumab' OR 'avelumab' OR 'durvalumab' OR 'tremelimumab'. Prospectives studies evaluating anti-PD(L)1 and anti-CTLA-4 monoclonal antibodies were included. RESULTS: Evidence-data related to early phase and phase III trials evaluating the 5 ICIs in the advanced urothelial carcinoma are detailed in this review. Anti-tumour activity of the 5 ICIs supporting the FDA approval in the second-line setting are reported. The activity of PD(L)1 inhibitors in the first-line setting in cisplatin-ineligible patients are also presented. Ongoing trials in earlier disease-states including non-muscle-invasive and muscle-invasive bladder cancer are discussed. CONCLUSIONS: Blocking the PD-1 negative immune receptor or its ligand, PD-L1, results in unprecedented rates of anti-tumour activity in patients with metastatic urothelial cancer. However, a large majority of patients do not respond to anti-PD(L)1 drugs monotherapy. Investigations exploring the potential value of predictive biomarkers, optimal combination and sequences are ongoing to improve such treatment strategies.

Testicle-sparing surgery versus radical orchiectomy in the management of Leydig cell tumors: results from a multicenter study.

OBJECTIVE: To compare the oncological outcomes of testicle-sparing surgery (TSS) and radical orchiectomy (RO) in patients with Leydig cell tumor (LCT) of the testis. PATIENTS AND METHODS: A multicenter retrospective clinical study was conducted in 12 centers in France. All the patients with histologically proven LCT were included and analyzed according to treatment (organ-sparing surgery or radical orchiectomy). Patients underwent preoperative clinical, biological and imaging assessment. Demographic, clinical, and pathological variables were collected at baseline and compared between groups according to surgical treatment. Follow-up was calculated using the reverse Kaplan-Meier estimation and was updated at the end of 2015. RESULTS: Between 1986 and 2014, 56 patients presented with LCT were identified and included in the study. Twenty-one patients (37.5%) underwent TSS and 35 (62.5%) RO. Demographics and tumor characteristics were not significantly different between the groups. Median follow-up was 62 months after TSS, but only 35 months after RO. Two patients (9.5%) developed local recurrence 15 and 34 months after TSS and underwent secondary RO. No local recurrence or metastasis was observed after complementary treatment. No recurrence was observed after RO. Disease-free survival did not differ between the groups (95.2% in TSS versus 77.1% in the RO group, p = 0.23). No patient died in the TSS group, but three patients (8.6%) in the RO group died from other diseases without evidence of relapse. One patient (4.8%) in the TSS group versus five (14.3%) in the RO group were lost to follow-up. CONCLUSION: Long-term follow-up suggests that testicle-sparing surgery does not compromise relapse-free survival in the treatment of Leydig cell tumor of the testis.

IGF-1R associates with adverse outcomes after radical radiotherapy for prostate cancer.

BACKGROUND: Activated type 1 insulin-like growth factor receptors (IGF-1Rs) undergo internalisation and nuclear translocation, promoting cell survival. We previously reported that IGF-1R inhibition delays DNA damage repair, sensitising prostate cancer cells to ionising radiation. Here we tested the clinical relevance of these findings. METHODS: We assessed associations between IGF-1R and clinical outcomes by immunohistochemistry in diagnostic biopsies of 136 men treated with 55-70 Gy external beam radiotherapy for prostate cancer, comparing results with publicly available transcriptional data in surgically treated patients. RESULTS: Following radiotherapy, overall recurrence-free survival was shorter in patients whose tumours contained high total, cytoplasmic and internalised (nuclear/cytoplasmic) IGF-1R. High total IGF-1R associated with high primary Gleason grade and risk of metastasis, and cytoplasmic and internalised IGF-1R with biochemical recurrence, which includes patients experiencing local recurrence within the radiation field indicating radioresistance. In multivariate analysis, cytoplasmic, internalised and total IGF-1R were independently associated with risk of overall recurrence, and cytoplasmic IGF-1R was an independent predictor of biochemical recurrence post radiotherapy. Insulin-like growth factor receptors expression did not associate with biochemical recurrence after radical prostatectomy. CONCLUSIONS: These data reveal increased risk of post-radiotherapy recurrence in men whose prostate cancers contain high levels of total or cytoplasmic IGF-1R.