Preparing for the Worst: Management and Predictive Factors of Open Conversion During Minimally Invasive Renal Tumor Surgery (UroCCR-135 Study).

Background and objective: Data regarding open conversion (OC) during minimally invasive surgery (MIS) for renal tumors are reported from big databases, without precise description of the reason and management of OC. The objective of this study was to describe the rate, reasons, and perioperative outcomes of OC in a cohort of patients who underwent MIS for renal tumor initially. The secondary objective was to find the factors associated with OC. Methods: Between 2008 and 2022, of the 8566 patients included in the UroCCR project prospective database (NCT03293563), who underwent laparoscopic or robot-assisted minimally invasive partial (MIPN) or radical (MIRN) nephrectomy, 163 experienced OC. Each center was contacted to enlighten the context of OC: "emergency OC" implied an immediate life-threatening situation not reasonably manageable with MIS, otherwise "elective OC". To evaluate the predictive factors of OC, a 2:1 paired cohort on the UroCCR database was used. Key findings and limitations: The incidence rate of OC was 1.9% for all cases of MIS, 2.9% for MIRN, and 1.4% for MIPN. OC procedures were mostly elective (82.2%). The main reason for OC was a failure to progress due to anatomical difficulties (42.9%). Five patients (3.1%) died within 90 d after surgery. Increased body mass index (BMI; odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.01-1.09, p = 0.009) and cT stage (OR: 2.22, 95% CI: 1.24-4.25, p = 0.008) were independent predictive factors of OC. Conclusions and clinical implications: In MIS for renal tumors, OC was a rare event (1.9%), caused by various situations, leading to impaired perioperative outcomes. Emergency OC occurred once every 300 procedures. Increased BMI and cT stage were independent predictive factors of OC. Patient summary: The incidence rate of open conversion (OC) in minimally invasive surgery for renal tumors is low. Only 20% of OC procedures occur in case of emergency, and others are caused by various situations. Increased body mass index and cT stage were independent predictive factors of OC.

Surgical management for penile fracture: A retrospective, observational, multicenter study.

INTRODUCTION: The objective of this study is to make an inventory of surgical practices and their consequences in the short and medium term on sexuality and micturition comfort. MATERIALS AND METHODS: It is a retrospective multicenter study over ten years on 63 men who had an operation for a fracture of the corpora cavernosa associated or not with a urethral lesion. Patient history, clinical presentation, surgical management as well as postoperative data were collected from operative reports. Residual penis curvature, IIEF5 score, IPSS score and residual pain were collected during a telephone interview during data collection. RESULTS: No statistically significant difference was demonstrated for IIEF5, IPSS, sequelae curvature, pain during intercourse, time to resumption of sexual life, rate of surgical resumption between use of absorbable or non-absorbable threads and between the realization of an overlock or a separate point. We found a significant difference in the time taken to resume sexual activity, between surgical exploration by degloving compared to elective surgical exploration. CONCLUSION: Our study shows great variability in the surgical management of penile fractures, with no influence in the short and medium term on sexuality and urination comfort. Medium-term complications such as erectile dysfunction, curvature of the penis and pain during sexual intercourse seem frequent and insufficiently diagnosed, but decrease during urological follow-up.

Cohort profile: COBLAnCE: a French prospective cohort to study prognostic and predictive factors in bladder cancer and to generate real-world data on treatment patterns, resource use and quality of life.

PURPOSE: Bladder cancer is a complex disease with a wide range of outcomes. Clinicopathological factors only partially explain the variability between patients in prognosis and treatment response. There is a need for large cohorts collecting extensive data and biological samples to: (1) investigate gene-environment interactions, pathological/molecular classification and biomarker discovery; and (2) describe treatment patterns, outcomes, resource use and quality of life in a real-world setting. PARTICIPANTS: COBLAnCE (COhort to study BLAdder CancEr) is a French national prospective cohort of patients with bladder cancer recruited between 2012 and 2018 and followed for 6 years. Data on patient and tumour characteristics, treatments, outcomes and biological samples are collected at enrolment and during the follow-up. FINDINGS TO DATE: We describe the cohort at enrolment according to baseline surgery and tumour type. In total, 1800 patients were included: 1114 patients with non-muscle-invasive bladder cancer (NMIBC) and 76 patients with muscle-invasive bladder cancer (MIBC) had transurethral resection of a bladder tumour without cystectomy, and 610 patients with NMIBC or MIBC underwent cystectomy. Most patients had a solitary lesion (56.3%) without basement membrane invasion (71.7% of Ta and/or Tis). Half of the patients with cystectomy were stage ≤T2 and 60% had non-continent diversion. Surgery included local (n=298) or super-extended lymph node dissections (n=11) and prostate removal (n=492). Among women, 16.5% underwent cystectomy and 81.4% anterior pelvectomy. FUTURE PLANS: COBLAnCE will be used for long-term studies of bladder cancer with focus on clinicopathological factors and molecular markers. It will lead to a much-needed improvement in the understanding of the disease. The cohort provides valuable real-world data, enabling researchers to study various research questions, assess routine medical practices and guide medical decision-making.

Persistent organic pollutants promote aggressiveness in prostate cancer.

Increasing evidence points towards a causal link between exposure to persistent organic pollutants (POPs) with increased incidence and aggressivity of various cancers. Among these POPs, dioxin and PCB-153 are widely found in our environment and represent a significant source of contamination. Dioxin exposure has already been linked to cancer such as non-Hodgkin's lymphoma, but remains to be more extensively investigated in other cancers. Potential implications of dioxin and PCB-153 in prostate cancer progression spurred us to challenge both ex vivo and in vivo models with low doses of these POPs. We found that dioxin or PCB-153 exposure increased hallmarks of growth and metastasis of prostate cancer cells ex vivo and in grafted NOD-SCID mice. Exposure induced histopathological carcinoma-like patterns in the Ptenpc-/- mice. We identified up-regulation of Acetyl-CoA Acetyltransferase-1 (ACAT1) involved in ketone bodies pathway as a potential target. Mechanistically, genetic inhibition confirmed that ACAT1 mediated dioxin effect on cell migration. Using public prostate cancer datasets, we confirmed the deregulation of ACAT1 and associated gene encoded ketone bodies pathway enzymes such as OXCT1, BDH1 and HMGCL in advanced prostate cancer. To further explore this link between dioxin and ACAT1 deregulation, we analyzed a unique prostate-tumour tissue collection from the USA veterans exposed to agent orange, known to be highly contaminated by dioxin because of industrial production. We found that ACAT1 histoscore is significantly increased in exposed patients. Our studies reveal the implication of dioxin and PCB-153 to induce a prometastatic programme in prostate tumours and identify ACAT1 deregulation as a key event in this process.

Artificial intelligence to improve cytology performance in urothelial carcinoma diagnosis: results from validation phase of the French, multicenter, prospective VISIOCYT1 trial.

PURPOSE: Cytology and cystoscopy, the current gold standard for diagnosing urothelial carcinomas, have limits: cytology has high interobserver variability with moderate or not optimal sensitivity (particularly for low-grade tumors); while cystoscopy is expensive, invasive, and operator dependent. The VISIOCYT1 study assessed the benefit of VisioCyt® for diagnosing urothelial carcinoma. METHODS: VISIOCYT1 was a French prospective clinical trial conducted in 14 centers. The trial enrolled adults undergoing endoscopy for suspected bladder cancer or to explore the lower urinary tract. Participants were allocated either Group 1: with bladder cancer, i.e., with positive cystoscopy or with negative cystoscopy but positive cytology, or Group 2: without bladder cancer. Before cystoscopy and histopathology, slides were prepared for cytology and the VisioCyt® test from urine samples. The diagnostic performance of VisioCyt® was assessed using sensitivity (primary objective, 70% lower-bound threshold) and specificity (75% lower-bound threshold). Sensitivity was also assessed by tumor grade and T-staging. VisioCyt® and cytology performance were evaluated relative to the histopathological assessments. RESULTS: Between October 2017 and December 2019, 391 participants (170 in Group 1 and 149 in Group 2) were enrolled. VisioCyt®'s sensitivity was 80.9% (95% CI 73.9-86.4%) and specificity was 61.8% (95% CI 53.4-69.5%). In high-grade tumors, the sensitivity was 93.7% (95% CI 86.0-97.3%) and in low-grade tumors 66.7% (95% CI 55.2-76.5%). Sensitivity by T-staging, compared to the overall sensitivity, was higher in high-grade tumors and lower in low-grade tumors. CONCLUSION: VisioCyt® is a promising diagnostic tool for urothelial cancers with improved sensitivities for high-grade tumors and notably for low-grade tumors.

Imaging quality of an artificial intelligence denoising algorithm: validation in 68Ga PSMA-11 PET for patients with biochemical recurrence of prostate cancer.

BACKGROUND: 68 Ga-PSMA PET is the leading prostate cancer imaging technique, but the image quality remains noisy and could be further improved using an artificial intelligence-based denoising algorithm. To address this issue, we analyzed the overall quality of reprocessed images compared to standard reconstructions. We also analyzed the diagnostic performances of the different sequences and the impact of the algorithm on lesion intensity and background measures. METHODS: We retrospectively included 30 patients with biochemical recurrence of prostate cancer who had undergone 68 Ga-PSMA-11 PET-CT. We simulated images produced using only a quarter, half, three-quarters, or all of the acquired data material reprocessed using the SubtlePET® denoising algorithm. Three physicians with different levels of experience blindly analyzed every sequence and then used a 5-level Likert scale to assess the series. The binary criterion of lesion detectability was compared between series. We also compared lesion SUV, background uptake, and diagnostic performances of the series (sensitivity, specificity, accuracy). RESULTS: VPFX-derived series were classified differently but better than standard reconstructions (p < 0.001) using half the data. Q.Clear series were not classified differently using half the signal. Some series were noisy but had no significant effect on lesion detectability (p > 0.05). The SubtlePET® algorithm significantly decreased lesion SUV (p < 0.005) and increased liver background (p < 0.005) and had no substantial effect on the diagnostic performance of each reader. CONCLUSION: We show that the SubtlePET® can be used for 68 Ga-PSMA scans using half the signal with similar image quality to Q.Clear series and superior quality to VPFX series. However, it significantly modifies quantitative measurements and should not be used for comparative examinations if standard algorithm is applied during follow-up.

Management and Outcome After Early Renal Transplant Vein Thrombosis: A French Multicentre Observational Study of Real-Life Practice Over 24 Years.

Early (<14 days) renal transplant vein thrombosis posttransplant (eRVTPT) is a rare but threatening complication. We aimed to assess eRVTPT management and the rate of functional renal transplantation. Of 11,172 adult patients who had undergone transplantation between 01/1997 and 12/2020 at 6 French centres, we identified 176 patients with eRVTPT (1.6%): 16 intraoperative (Group 1, G1) and 160 postoperative (Group 2, G2). All but one patient received surgical management. Patients in group G2 had at least one imaging test for diagnostic confirmation (N = 157, 98%). During the operative management of the G2 group, transplantectomy for graft necrosis was performed immediately in 59.1% of cases. In both groups, either of two techniques was preferred, namely, thrombectomy by renal venotomy or thrombectomy + venous anastomosis repair, with no difference in the functional graft rate (FGR) at hospital discharge (p = NS). The FGR was 62.5% in G1 and 8.1% in G2 (p < 0.001). Numerous complications occurred during the initial hospitalization: 38 patients had a postoperative infection (21.6%), 5 experienced haemorrhagic shock (2.8%), 29 exhibited a haematoma (16.5%), and 97 (55.1%) received a blood transfusion. Five patients died (2.8%). Our study confirms the very poor prognosis of early renal graft venous thrombosis.

Low temperature pyrolytic biochar is a preferred choice for sulfonamide-Cu(II) contaminated soil remediation in tropical climate region.

Biochar is getting increasing consideration for eco-friendly soil amendment and environmental remediation. Once added to the soil, biochar would undergo the natural ageing process, affecting its physicochemical properties and, as a result, the adsorption and immobilization of pollutants in the water and soil. To evaluate the high/low temperature pyrolyzed biochar performance on complex contaminants and the effect of climate ageing, the batch experiments were conducted on the adsorption of the pollutants of antibiotics sulfapyridine (SPY) and a typical coexisting heavy metal Cu2+ as one or binary system on low/high pyrolytic temperature biochars before and after the simulated tropical climate and frigid climate region ageing treatment. The results showed that high-temperature ageing could enhance the SPY adsorption in biochar-amended soil. The SPY sorption mechanism was fully elucidated, and the result confirmed that H-bonding was the dominant role in biochar-amended soil, and π-π electron-donor-acceptor (EDA) interaction and micro-pore filling was another factor for SPY adsorption. This study could lead to the conclusion that low-temperature pyrolytic biochar is a better option for sulfonamide-Cu(II) contaminated soil remediation in tropical regions.

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.

N-doped and activated porous biochar derived from cocoa shell for removing norfloxacin from aqueous solution: Performance assessment and mechanism insight.

Environmental pollution has worsened as a result of antibiotic overuse. Nitrogen doping of biochar increases its ability to adsorb antibiotics and has been widely applied as an adsorbent. In this study, we synthesized nitrogen-doped biochar (N-A) from cocoa shell wastes calcined with urea and sodium bicarbonate (NaHCO3) as nitrogen sources and green activators, respectively. An analysis of the biochar morphology, structure, specific surface area, and functional groups provided an understanding of its properties. As indicated by increased surface area, micropores, and surface functional groups, biochar was enhanced in its performance for norfloxacin adsorption when activated using NaHCO3 and nitrogen doped. Adsorption experiments revealed that N-A biochar at 700 and 400 °C had a high adsorption capacity for NOR of 134 mg/g (N-A-CSB700) and 112.31 mg/g (N-A-CSB400) when compared to pristine biochar at 59.27 mg/g (CSB700) and 56.34 mg/g (CSB400), indicating that N-A doped modification on biochar greatly improved adsorption capacity. The Langmuir model demonstrated better NOR adsorption isotherms. The pseudo-second order and Elovich models closely followed the adsorption kinetics. Further investigations were conducted to determine how environmental factors influence biochar interaction with NOR. The results indicated a stable NOR removal efficiency was kept at a wide pH range, whereas the ionic strength inhibited the NOR adsorption process. The investigation into the sorption mechanism revealed that pore filling, H-bonding, π-π EDA interactions, ion exchange, and electrostatic attraction may all be implicated in the NOR adsorption process. Specifically, pore filling played the dominant role for N-A-CSB700, while N-A-CSB400 sorption occurred mainly via H-bonding. Since N-A-CSB700 doped biochar combines high adsorption capacity with a low inhibition effect of environmental factors (Na+/Ca2+), it has a high potential for future practical applications as an environmentally sustainable alternative. It uses low-cost solid waste to produce an adsorbent to cope with emerging contaminants such as antibiotics.

Effects of GSK-J4 on JMJD3 Histone Demethylase in Mouse Prostate Cancer Xenografts.

BACKGROUND/AIM: Histone methylation status is required to control gene expression. H3K27me3 is an epigenetic tri-methylation modification to histone H3 controlled by the demethylase JMJD3. JMJD3 is dysregulated in a wide range of cancers and has been shown to control the expression of a specific growth-modulatory gene signature, making it an interesting candidate to better understand prostate tumor progression in vivo. This study aimed to identify the impact of JMJD3 inhibition by its inhibitor, GSK4, on prostate tumor growth in vivo. MATERIALS AND METHODS: Prostate cancer cell lines were implanted into Balb/c nude male mice. The effects of the selective JMJD3 inhibitor GSK-J4 on tumor growth were analyzed by bioluminescence assays and H3K27me3-regulated changes in gene expression were analyzed by ChIP-qPCR and RT-qPCR. RESULTS: JMJD3 inhibition contributed to an increase in tumor growth in androgen-independent (AR-) xenografts and a decrease in androgen-dependent (AR+). GSK-J4 treatment modulated H3K27me3 enrichment on the gene panel in DU-145-luc xenografts while it had little effect on PC3-luc and no effect on LNCaP-luc. Effects of JMJD3 inhibition affected the panel gene expression. CONCLUSION: JMJD3 has a differential effect in prostate tumor progression according to AR status. Our results suggest that JMJD3 is able to play a role independently of its demethylase function in androgen-independent prostate cancer. The effects of GSK-J4 on AR+ prostate xenografts led to a decrease in tumor growth.

Impact of obesity in kidney transplantation: a prospective cohort study from French registries between 2008 and 2014.

BACKGROUND: The access of obese patients to kidney transplantation is limited despite several studies showing that obese transplant recipients had a better survival rate than those undergoing dialysis. The aim of this study was to compare patient and graft survival rates and post-renal transplant complications in obese patients and non-obese patients and to assess the effect of pre-transplant weight loss in obese patients on transplant outcomes. METHODS: We carried out a prospective cohort study using two French registries, the Renal Epidemiology and Information Network and CRISTAL, on 7270 kidney transplant patients between 2008 and 2014 in France. We compared obese patients with non-obese patients and obese patients who lost more than 10% of weight before the transplant (obese WL and obese nWL). RESULTS: The mean BMI in our obese patients was 32 kg/m2. Graft survival was lower in obese patients than in non-obese patients {hazard ratio (HR) = 1.40, [95% confidence interval (95% CI) 1.09; 1.78], P = 0.007}, whereas patient survival was similar [HR = 0.94, (95% CI 0.73; 1.23), P = 0.66]. Graft survival was significantly lower in obese WL than in obese nWL [HR = 2.17, (1.02; 4.63), P = 0.045], whereas patient survival was similar in the two groups [HR = 0.79, (0.35; 1.77), P = 0.56]. CONCLUSION: Grade 1 obesity does not seem to be a risk factor for excess mortality after kidney transplantation and should not be an obstacle to having access to a graft. Weight loss before a kidney transplant in these patients should not be essential for registration on waiting list.

Artificial intelligence to improve cytology performances in bladder carcinoma detection: results of the VisioCyt test.

OBJECTIVE: To explore the utility of artificial intelligence (AI) using the VisioCyt® test (VitaDX International, Rennes, France) to improve diagnosis of bladder carcinoma using voided urine cytology. PATIENTS AND METHODS: A national prospective multicentre trial (14 centres) was conducted on 1360 patients, divided in two groups. The first group included bladder carcinoma diagnosis with different histological grades and stages, and the second group included control patients based on negative cystoscopy and cytology results. The first step of this VISIOCYT1 trial focussed on algorithm development and the second step on validating this algorithm. A total of 598 patients were included in this first step, 449 patients with bladder tumours (219 high-grade and 230 low-grade) and 149 as negative controls. The VisioCyt test was compared to voided urine cytology performed by experienced uro-pathologists from each centre. RESULTS: Overall sensitivity was highly improved by the VisioCyt test compared to cytology (84.9% vs 43%). For high-grade tumours the VisioCyt test sensitivity was 92.6% vs 61.1% for the uro-pathologists. Regarding low-grade tumours, VisioCyt test sensitivity was 77% vs 26.3% for the uro-pathologists. CONCLUSION: In comparison to routine cytology, the results of the first phase of the VISIOCYT1 trial show very clear progress in terms of sensitivity, which is particularly visible and interesting for low-grade tumours. If the validation cohort confirms these results, it could lead to the VisioCyt test being considered as a very useful aid for pathologists. Moreover, as this test is in fact software based on AI, it should become more and more efficient as more data are collected.

The role of CT-scan assessment of muscle mass in predicting postoperative surgical complications after renal transplantation.

PURPOSE: Despite a high rate of undernutrition in renal transplantation recipients, prognostic value of sarcopenia remains unclear. We evaluated the relation between sarcopenia and post-operative outcomes after renal transplantation. METHODS: During 7 years, each patient who underwent renal transplantation was retrospectively included. Patients with no recent pre-operative CT-scan were excluded. Sarcopenia was evaluated by measuring the muscle surface area on CT-scan section passing through the third lumbar vertebra. Main outcomes were post-operative complications at 1 month and 1 year according to the Clavien-Dindo classification. RESULTS: Overall, 102 patients were included. One month of complication rate was 63.9%. At 1 year, 60.8% experienced at least one medical complication and 29.4% one surgical complication. At 1 year post transplantation, low muscle density on CT scan was a surgical complication risk factor (OR = 0.6, 95% CI = [0.3-0.9], p = 0.05). The area under the curve of a 1-year complication predictive model including muscle density was 0.64. We did not observe significant relationship between CT-scan sarcopenia indicator and 1-month post-transplantation complication. CONCLUSION: Although no clear link between sarcopenia and complications was exhibited in our study, low CT-scan muscle density was associated with 1-year surgical complications. The role of muscle density and its relation with sarcopenia and post-transplantation outcomes should be further explored.

O/N/P-doped biochar induced to enhance adsorption of sulfonamide with coexisting Cu2+/ Cr (VI) by air pre-oxidation.

The aim of this work to study the effectiveness of newly synthesized O/N/P-doped biochar for the removal of antibiotics with coexisting heavy metals. This study developed a low-dose additive agent with air pre-oxidation (APO) to obtain O/N/P-doped biochar (ONPBC) at 650/350 °C pyrolysis temperature with adsorption amount of 76.99 mg·g-1 (ONPBC650) and 62.33 mg·g-1 (ONPBC350) for sulfapyridine (SPY), comparing to pristine biochar 9.25 mg·g-1 (BC650) and 11.60 mg·g-1 (BC350), indicating the adsorption capacity of biochar has been greatly improved after modification. The main sorption mechanisms were elucidated for ONPBC650 (surface physical sorption) and ONPBC350 (H-bonding). The coexisting Cu2+/Cr (VI) showed different inhibition effects on the adsorption of SPY by ONPBC650/350. Considering a trade-off between high adsorption capacity and low inhibition effect of coexisting heavy metals, economic low-temperature O/N/P-doped biochar such as ONPBC350 could be a preferred adsorbent for the removal of sulfonamide or similar organic pollutants from contaminated water.

Sunitinib Alone or After Nephrectomy for Patients with Metastatic Renal Cell Carcinoma: Is There Still a Role for Cytoreductive Nephrectomy?

BACKGROUND: The CARMENA trial in patients with metastatic renal cell carcinoma (mRCC) demonstrated that treatment with sunitinib alone was noninferior to cytoreductive nephrectomy (CN) followed by sunitinib (nephrectomy⬜sunitinib). OBJECTIVE: The objective of this study was to provide updated overall survival (OS) outcomes of CARMENA and assess whether some subgroups may still benefit from upfront CN. DESIGN, SETTING, AND PARTICIPANTS: CARMENA was a phase III trial in 450 patients with mRCC enrolled from 2009 to 2017. INTERVENTION: Patients in the intention-to-treat population received nephrectomy⬜sunitinib (standard of care [SOC]; n = 226) or sunitinib alone (n = 224). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoint was OS, assessed using an updated data cut-off (October 2018; median OS event-free follow-up, 36.6 mo). Patients were reclassified by risk using International Metastatic RCC Database Consortium (IMDC) criteria. RESULTS AND LIMITATIONS: Sunitinib alone was noninferior to nephrectomy⬜sunitinib (hazard ratio [HR], 0.97; 95% confidence interval, 0.79⬜1.19; p = 0.8) and demonstrated longer median OS (19.8 mo vs 15.6 mo, respectively). For patients with two or more IMDC risk factors, OS was significantly longer with sunitinib alone than with nephrectomy⬜sunitinib (31.2 mo vs 17.6 mo, respectively; HR, 0.65; p = 0.03). For patients with one IMDC risk factor, OS was longer for nephrectomy⬜sunitinib versus sunitinib alone although not significantly (31.4 mo vs 25.2 mo; HR, 1.30; p = 0.2). The post hoc nature of the subgroup analyses may limit their interpretation. CONCLUSIONS: Sunitinib alone was noninferior compared with nephrectomy⬜sunitinib, suggesting that CN should not be considered SOC in patients with mRCC requiring systemic treatment. Certain subgroups, including patients with one IMDC risk factor, may still benefit from upfront CN. PATIENT SUMMARY: We assessed the survival of patients with metastatic kidney cancer in a clinical trial. Patients treated with sunitinib on its own had the same survival as patients who had surgery before sunitinib treatment. We conclude that surgery may not be necessary for some patients with metastatic kidney cancer.

Apalutamide, darolutamide and enzalutamide in nonmetastatic castration-resistant prostate cancer: a meta-analysis.

Aim: Comparison of the efficacy/safety/health-related quality of life of apalutamide, enzalutamide and darolutamide in Phase III clinical trials involving patients with nonmetastatic castration-resistant prostate cancer was performed. Materials & methods: Relevant studies were identified by searching PubMed as well as conference abstracts reporting updated overall survival. Three pivotal trials were identified, SPARTAN (apalutamide), PROSPER (enzalutamide) and ARAMIS (darolutamide), and form the basis of this analysis. Results: All three drugs significantly prolonged metastasis-free survival, prostate-specific antigen response and overall survival versus placebo, and were generally well tolerated. Conclusion: Drug selection will likely be influenced by tolerability/safety and other factors, such as the propensity for drug-drug interactions and the presence of comorbidities, that affect the risk-benefit balance in individual patients.

The Functions of the Demethylase JMJD3 in Cancer.

Cancer is a major cause of death worldwide. Epigenetic changes in response to external (diet, sports activities, etc.) and internal events are increasingly implicated in tumor initiation and progression. In this review, we focused on post-translational changes in histones and, more particularly, the tri methylation of lysine from histone 3 (H3K27me3) mark, a repressive epigenetic mark often under- or overexpressed in a wide range of cancers. Two actors regulate H3K27 methylation: Jumonji Domain-Containing Protein 3 demethylase (JMJD3) and Enhancer of zeste homolog 2 (EZH2) methyltransferase. A number of studies have highlighted the deregulation of these actors, which is why this scientific review will focus on the role of JMJD3 and, consequently, H3K27me3 in cancer development. Data on JMJD3's involvement in cancer are classified by cancer type: nervous system, prostate, blood, colorectal, breast, lung, liver, ovarian, and gastric cancers.

Randomized Phase III Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin, or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients with Muscle-invasive Bladder Cancer. Analysis of the GETUG/AFU V05 VESPER Trial Secondary Endpoints: Chemotherapy Toxicity and Pathological Responses.

BACKGROUND: Perioperative chemotherapy (neoadjuvant or adjuvant) has been developed to increase overall survival for nonmetastatic muscle-invasive bladder cancer (MIBC). Retrospective studies or prospective phase II trials have been reported to use dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC). As dd-MVAC has shown higher response rates in metastatic disease, better efficacy is expected in the perioperative setting. OBJECTIVE: We designed a randomized phase III trial to compare the efficacy of dd-MVAC or GC in MIBC perioperative (neoadjuvant or adjuvant) setting. DESIGN, SETTING AND PARTICIPANTS: A total of 500 patients were randomized from February 2013 to March 2018 in 28 centers and received either six cycles of dd-MVAC every 2 wk or four cycles of GC every 3 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint (progression-free survival at 3 yr) was not reported. We focused on secondary endpoints: chemotherapy toxicity and pathological responses. RESULTS AND LIMITATIONS: In the neoadjuvant group, 218 patients received dd-MVAC and 219 received GC. Of the patients, 60% received six cycles in the dd-MVAC arm and 84% received four cycles in the GC arm; 199 (91%) and 198 (90%) patients underwent surgery, respectively. Complete pathological response (ypT0pN0) was observed in 84 (42%) and 71 (36%) patients, respectively (p=0.2). An organ-confined status (