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Neutrophil extracellular traps (NET) have been implicated in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Here, we developed a novel, label-free, high-throughput bio-impedance technique to effectively measure serum NET-inducing activity. Using this technique, NET-inducing activity of serum derived from patients with AAV was assessed in a prospective cohort of 62 patients presenting with active AAV with major organ involvement. Thirty-five patients presented with new and 27 patients presented with relapsing AAV, of whom 38 had kidney and/or 31 had lung involvement. NET-inducing activity was assessed at diagnosis of active AAV (time zero), during the first 6 weeks of treatment, and after 6 months of treatment. Forty-seven patients revealed elevated NET-inducing activity at time zero. After initiation of immunosuppressive treatment, NET-inducing activity was reduced at six weeks. A subsequent increase at six months could potentially identify patients with relapsing disease (hazard ratio, 11.45 [interquartile range 1.36-96.74]). NET-inducing activity at time zero correlated with kidney function and proteinuria. Importantly, in kidney tissue, NETs co-localized with lesions typical of ANCA-associated glomerulonephritis and even correlated with systemic serum NET-inducing activity. Thus, our prospective data corroborate the importance of NET formation in AAV and ANCA-associated glomerulonephritis and the potential of longitudinal evaluation, as monitored by our novel bio-impedance assay and detailed histological evaluation.

Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a randomized controlled trial.Setting & Participants: Participants in the CREDENCE trial.Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kidney failure, doubling of serum creatinine concentration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (Results: The mean age of the cohort was 63.0 ± 9.2 years, and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.48-0.82], and 0.89 [0.61-1.29] for ages Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.

Introduction There is a substantial risk of developing stenosis and dysfunction in the arteriovenous fistula (AVF) in patients on hemodialysis (HD). Far infrared radiation (FIR) is a non-invasive local intervention with a potentially beneficial effect on AVF patency. The underlying mechanism is not clear. It was hypothesized that a single FIR treatment reduces factors of inflammation and promotes endothelial vasodilators in the AVF. Methods Forty HD patients with an AVF were included in an open-label intervention study. Patients were randomized to receive either FIR (FIR group) or no FIR (control group). Blood samples were drawn directly from the AVF and from a peripheral vein in the non-AVF arm before (T0) and 40 min after (T40) treatment during a HD session. The changes [median (interquartile range)] in circulating factors of inflammation, endothelial function and vasoreactivity during FIR were measured. Results In the AVF a single FIR treatment during dialysis resulted in a significantly diminished decrease in soluble vascular cell adhesion molecule, sVCAM [−31.6 (−54.3; 22.1) vs −89.9 (−121.6; −29.3), P = .005] and soluble intercellular adhesion molecule, sICAM [−24.2 (−43.5; 25.3) vs −49 (−79.9; −11.6), P = .02] compared with the control group. Other factors, such as interleukins, nitrite, nitrate and tumor necrosis factor 1, also declined during dialysis, but with no significant differences related to FIR in either the AVF or the non-AVF arm. Conclusion A single FIR treatment attenuated the decrease in sVCAM and sICAM in the AVF compared with a control group during HD. Findings do not support the hypothesis of a vaso-protective effect of FIR. The long-term effects of FIR on the AVF are unknown.

Background In maintenance hemodialysis patients, intradialytic hypotension (IDH) is a frequent complication that has been associated with poor clinical outcomes. Prediction of IDH may facilitate timely interventions and eventually reduce IDH rates. Methods We developed a machine learning model to predict IDH in in-center hemodialysis patients 15–75 min in advance. IDH was defined as systolic blood pressure (SBP) Results We utilized data from 693 patients who contributed 42 656 hemodialysis sessions and 355 693 intradialytic SBP measurements. IDH occurred in 16.2% of hemodialysis treatments. Our model predicted IDH 15–75 min in advance with an AUROC of 0.89. Top IDH predictors were the most recent intradialytic SBP and IDH rate, as well as mean nadir SBP of the previous 10 dialysis sessions. Conclusions Real-time prediction of IDH during an ongoing hemodialysis session is feasible and has a clinically actionable predictive performance. If and to what degree this predictive information facilitates the timely deployment of preventive interventions and translates into lower IDH rates and improved patient outcomes warrants prospective studies.

Background The current childhood obesity pandemic is likely to result in an increased risk of chronic kidney disease (CKD) later in life. Correlations between obesity-related comorbidities and kidney function can be found, but it is unclear to what extent this is caused by bias due to different mathematical forms of the estimated glomerular filtration rate (eGFR) equations. The present study aimed to analyze correlations between obesity-related comorbidities and different eGFR equations and to investigate whether rescaled serum creatinine (SCr/Q) for sex and age or height might be an alternative biomarker for kidney function estimation. Methods This cross-sectional cohort study included 600 children with overweight and obesity. Mean age was 12.20 ± 3.28 years, 53.5% were female, and mean BMI z-score was 3.31 ± 0.75. All children underwent a comprehensive assessment that included anthropometrical and blood pressure measurements, laboratory examination, air displacement plethysmography, and polysomnography. Qage and Qheight polynomials were used to rescale SCr and multiple creatinine-based eGFR equations were compared. Results SCr/Q and almost all GFR estimations significantly correlated with a waist-to-hip ratio, fat mass, homeostasis model assessment for insulin resistance, and triacylglyceride, HDL cholesterol, alanine transaminase, and serum uric acid concentrations. Multiple correlations, however, were not confirmed by all equations, which suggests dependency on the mathematical form of the different eGFR equations. Conclusions Correlations between obesity-related comorbidities and creatinine-based eGFR are present in children with overweight and obesity, but depend to a large extent on the eGFR equation of choice. SCr/Q might be an alternative biomarker for assessing correlations between obesity-related comorbidities and kidney function in children with overweight and obesity. Graphical Abstract

In anti-neutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV), hematuria and proteinuria are biomarkers reflecting kidney involvement at diagnosis. Yet, the prognostic value of their persistence after immunosuppressive induction therapy, reflecting kidney damage or persistent disease, remains uncertain. To study this, our post hoc analysis included participants of five European randomized clinical trials on AAV (MAINRITSAN, MAINRITSAN2, RITUXVAS, MYCYC, IMPROVE). Urine protein-creatinine ratio (UPCR) and hematuria of spot urine samples collected at the end of induction therapy (four-six months after treatment initiation) were correlated with the occurrence of a combined end point of death and/or kidney failure, or relapses during follow-up. Among 571 patients (59% men, median age 60), 60% had anti–proteinase 3-ANCA and 35% had anti–myeloperoxidase-ANCA, while 77% had kidney involvement. After induction therapy, 157/526 (29.8%) had persistent hematuria and 165/481 (34.3%) had UPCR of 0.05 g/mmol or more. After a median follow-up of 28 months (interquartile range 18-42), and adjustment for age, ANCA type, maintenance therapy, serum creatinine and persistent hematuria after induction, a UPCR of 0.05 g/mmol or more after induction was associated with significant risk of death/kidney failure (adjusted Hazard Ratio [HR] 3.06, 95% confidence interval 1.09-8.59) and kidney relapse (adjusted subdistribution HR 2.22, 1.16-4.24). Persistent hematuria was associated with significant kidney relapse (adjusted subdistribution HR 2.16, 1.13-4.11) but not with relapse affecting any organ nor with death/kidney failure. Thus, in this large cohort of patients with AAV, persistent proteinuria after induction therapy was associated with death/kidney failure and kidney relapse, whereas persistent hematuria was an independent predictor of kidney relapse. Hence, these parameters must be considered to assess long-term kidney prognosis of patients with AAV.

Morphological alterations at the kidney filtration barrier increase intrinsic capillary wall permeability resulting in albuminuria. However, automated, quantitative assessment of these morphological changes has not been possible with electron or light microscopy. Here we present a deep learning-based approach for segmentation and quantitative analysis of foot processes in images acquired with confocal and super-resolution fluorescence microscopy. Our method, Automatic Morphological Analysis of Podocytes (AMAP), accurately segments podocyte foot processes and quantifies their morphology. AMAP applied to a set of kidney diseases in patient biopsies and a mouse model of focal segmental glomerulosclerosis allowed for accurate and comprehensive quantification of various morphometric features. With the use of AMAP, detailed morphology of podocyte foot process effacement was found to differ between categories of kidney pathologies, showed detailed variability between diverse patients with the same clinical diagnosis, and correlated with levels of proteinuria. AMAP could potentially complement other readouts such as various omics, standard histologic/electron microscopy and blood/urine assays for future personalized diagnosis and treatment of kidney disease. Thus, our novel finding could have implications to afford an understanding of early phases of kidney disease progression and may provide supplemental information in precision diagnostics.

Atherosclerotic renovascular disease is the most frequent cause of renovascular hypertension and its prevalence increases with age and in specific subset of patients, such as those with end-stage chronic kidney disease, heart failure, and coronary artery disease. Besides hypertension, atherosclerotic renovascular disease is responsible for several clinical manifestations, including life-threatening conditions, such as recurrent flash pulmonary edema, rapidly progressive chronic kidney disease, or acute kidney injury. Atherosclerotic renovascular disease is usually part of a more diffuse atherosclerotic process and requires a combination therapy including antihypertensive, antiplatelet and lipid-lowering agents, as well as optimization of antidiabetic treatment, if needed. Besides medical therapy, percutaneous renal angioplasty was supposed to be the most effective therapy for atherosclerotic renovascular disease, by leading to blood flow restoration. However, despite an apparently solid rationale, several randomized clinical trials failed to confirm the favorable effects of percutaneous renal angioplasty on blood pressure control, kidney function, cardiovascular and renal outcomes, previously reported in observational, retrospective and single-center cohorts, switching off the enthusiasm for this procedure. Several studies’ limitations may partly account for this failure, including heterogeneity of diagnostic techniques, overestimation of the degree of renal artery stenosis, inappropriate timing of revascularization, multiple protocol revisions, frequent crossovers, and most importantly exclusion of patients at higher likelihood to respond to angioplasty. The purpose of this review is to summarize studies’ potential weaknesses and provide guidance to the clinician for identification of patients who may benefit most from revascularization.

BackgroundCOVID-19 is a complex multisystem disease, frequently associated with kidney injury. Since the beginning of the COVID-19 pandemic, we observed a striking increase in the incidence of acute tubulointerstitial nephritis (aTIN) without or with uveitis (TINUs) among children. This prompted us to examine whether SARS-CoV-2 might be the underlying trigger.MethodsWe conducted a French nationwide retrospective cohort study. We included all consecutive children diagnosed with aTIN or TINUs of undetermined cause between April-2020 and March-2021. SARS-CoV-2 antibody responses were tested by a luciferase immunoprecipitation system and compared to age-matched controls. Immunohistochemistry, immunofluorescence and molecular microbiology analyses were performed on kidney biopsies.ResultsForty-eight children were included with a median age at diagnosis of 14.7 years (9.4-17.6). aTIN and TINUs incidence rates increased 3-fold and 12-fold, respectively, compared to pre-pandemic years. All patients had impaired kidney function with a median eGFR of 31.9 ml/min/1.73m² at diagnosis. Kidney biopsies showed lesions of acute tubulointerstitial nephritis and 25% of patients had fibrosis. No patient had concomitant acute COVID-19. All 16 children tested had high anti-N IgG titers and one had anti-S IgGs. Next-generation sequencing failed to detect any infectious agents in kidney biopsies. However, SARS-CoV-2 RNA was detected by PCR in two kidney samples supporting a potential direct link between SARS-CoV-2 and aTIN/TINUs.ConclusionsWe describe a novel form of post-acute COVID-19 syndrome in children, unique in its exclusive kidney and eye involvement, and its distinctive anti-SARS-CoV-2 N+/S-serological profile. Our results support a causal association linking SARS-CoV-2 infection to this newly-reported burst of renal/eye inflammation.

Background: Bilateral kidney stones are commonly treated in staged procedures. Objective: To evaluate outcomes after same-sitting bilateral retrograde intrarenal surgery (SSB-RIRS) for renal stones. Design, setting, and participants: Data from adults who underwent bilateral RIRS in 21 centers were retrospectively reviewed (from January 2015 to June 2022). The inclusion criteria were unilateral/bilateral symptomatic bilateral stone(s) of any size/location in both kidneys and bilateral stones on follow-up with symptom/stone progression. Stone-free rate (SFR) was defined as absence of any fragment >3 mm at 3 mo. Outcome measurements and statistical analysis: Continuous variables are presented as medians and 25–75th percentiles. A multivariable logistic regression analysis was performed to evaluate independent predictors of sepsis and bilateral SFR. Results and limitations: A total of 1250 patients were included. The median age was 48.0 (36–61) yr. Of the patients, 58.2% were prestented. The median stone diameter was 10 mm on both sides. Multiple stones were present in 45.3% and 47.9% of the left and right kidneys, respectively. Surgery was stopped in 6.8% of cases. The median surgical time was 75.0 (55–90) min. Complications were transient fever (10.7%), fever/infection needing prolonged stay (5.5%), sepsis (2%), and blood transfusion (1.3%). Bilateral and unilateral SFRs were 73.0% and 17.4%, respectively. Female (odds ratio [OR] 2.97, 95% confidence interval [CI] 1.18–7.49, p = 0.02), no antibiotic prophylaxis (OR 5.99, 95% CI 2.28–15.73, p < 0.001), kidney anomalies (OR 5.91, 95% CI 1.96–17.94, p < 0.001), surgical time ≥100 min (OR 2.86, 95% CI 1.12–7.31, p = 0.03) were factors associated with sepsis. Female (OR 1.88, 95% CI 1.35–2.62, p < 0.001), bilateral prestenting (OR 2.16, 95% CI 1.16–7.66, p = 0.04), and the use of high-power holmium:YAG laser (OR 1.63, 95% CI 1.14–2.34, p < 0.01) and thulium fiber laser (OR 2.50, 95% CI 1.32–4.74, p < 0.01) were predictors of bilateral SFR. Limitations were retrospective study and no cost analysis. Conclusions: SSB-RIRS is an effective treatment with an acceptable complication rate in selected patients with kidney stones. Patient summary: In this large multicenter study, we looked at outcomes after same-sitting bilateral retrograde intrarenal surgery (SSB-RIRS) for renal stones in a large cohort. We found that SSB-RIRS was associated with acceptable morbidity and good stone clearance after a single session.

This study is about confirming the distribution of Lycopus exaltatus (Lamiaceae) in Türkiye, for which there is no reliable information about its existence in Türkiye. In addition, the description of L. exalatus, besides the ecology information in the area where it spreads; differences with Lycopus europaeus, whose distribution is known in Türkiye, are also emphasized.

Objective: To evaluate the effectiveness and safety profile of the tyrosine kinase inhibitor Axitinib for patients with advanced or metastatic renal cell carcinoma (a/mRCC) in a real-world setting. Methods: Adult patients from the German non-interventional post-approval multicenter STAR-TOR registry with a/mRCC (NCT00700258) were included if treated with Axitinib in second line or beyond. Overall survival (OS), progression-free survival (PFS) and adverse events were evaluated across subgroups using descriptive statistics and survival analyses. Results: Between November 2012 and December 2020, 75 study sites recruited 210 patients treated with Axitinib (69,6% male; median age 69 years; median Karnofsky Index 80%). Clear cell RCC was the most frequent histological subtype (81.0%). Axitinib was administered as second-line in 51.4%, third-line in 24.8%, and fourth-line treatment and beyond in 23.8% of the patients, respectively. MSKCC score was 15.0% favorable, 33.6% intermediate, and 51.3% poor risk. Median PFS was 5.6 months, and median OS 18.3 months. Patients with lactate dehydrogenase (LDH) levels > 300U/l had a nominally significantly shorter OS than patients with LDH≤300U/l (8.2 vs. 19.0 months, p = 0.008). Drug related adverse and serious adverse events were reported in 56.7% and 17.6% of the patients, respectively (most common adverse event: gastrointestinal disorders; 37.6%). Conclusions: This real-world study confirms the clinical relevance of Axitinib in the second-line and beyond setting for a/mRCC with OS and PFS reported in concordance with pivotal trials, while demonstrating a favorable safety profile. A high LDH serum level could be a negative predictive marker for Axitinib effectiveness, which can aid in clinical decision making.

BACKGROUND: The influence of age and comorbidities during decision-making for patients with renal cell carcinoma remains controversial. OBJECTIVE: To comprehensively review the available evidence regarding the impacts of age and comorbidities on the decision to perform partial nephrectomy (PN). EVIDENCE ACQUISITION: A systematic review was conducted in accordance with PRISMA and registered with PROSPERO (CRD42022344759). Only randomized control trials, prospective cohort studies, registry-based studies, or single/multi-institutional retrospective cohort studies comparing PN to other therapeutic options for cT1N0M0 renal masses were considered. The primary outcome was to assess differences in patients’ baseline characteristics between different treatments in order to investigate how those aspects have influenced clinical decision-making. Finally, perioperative outcomes were compared across the different options. EVIDENCE SYNTHESIS: Overall, patients who underwent PN were 3 to 11 years younger than those who underwent other treatments. Baseline renal function was slightly better in patients who underwent PN than in those who underwent radical nephrectomy (RN), active surveillance (AS), or tumor ablation. Patients undergoing PN had an average pre-treatment eGFR 4 to 6 points (mL/min/1.73 m2) higher than patients undergoing RN or tumor ablation. Likewise, the proportion of baseline chronic kidney disease (CKD) before treatment was higher in patients undergoing other treatments, with a rate of CKD between 6% and 56% higher compared with that for PN. A slightly higher proportion of baseline diabetes mellitus (DM) and cardiovascular comorbidities (CVD) were found in patients who underwent PN than in those who underwent RN (20% vs. 21% for DM and 37% vs. 41% for CVD). On average, patients who underwent AS and tumor ablation had more comorbidities, in terms of Charlson comorbidity index (CCI), DM, and CVD (50% vs. 38% for CCI ≥2; 25% vs. 20% for DM; and 43% vs. 37% for CVD). In terms of Eastern Cooperative Oncology Group (ECOG) Performance Status and American Society of Anesthesiologists (ASA) classification, no major differences were found between PN and other treatments, but a trend emerged whereby more fit patients underwent PN compared with RN (16% of ECOG >1 for PN vs. 18% for RN and 15% of ASA grade ≥3 for PN vs. 26% for RN). Again, tumor ablation was preferred for less fit patients (31% of ASA grade ≥3). No study included in our systematic review reported the baseline frailty status of patients treated for cT1 renal masses. The rates of perioperative complications and length of hospital stay (LOS) were similar between different techniques. CONCLUSIONS: Patients who underwent PN tended to be younger and fitter than those who underwent other available treatments for cT1 renal masses. Since this technique aims at reducing renal function impairment after surgery, a greater effort should be made to optimize patient selection to include more comorbid patients for whom PN might be useful.

BACKGROUND: The historical standard of care for locally advanced renal cell carcinoma (RCC) is nephrectomy + active surveillance. Despite a high recurrence rate ( 40% ), adjuvant therapy was previously not included in the standard of care. This review of adjuvant pharmacotherapy reflects conflicting results from multiple trials. OBJECTIVE: The objective of this review is to summarize the efficacy of therapy vs surveillance in resected early-stage intermediate to high-risk renal cell carcinoma. METHODS: We performed a systematic literature search using PubMed, EMBASE, and SCOPUS. Keywords such as “renal cell carcinoma”, “adjuvant therapy” and “nephrectomy” were used. In the literature search, 2,711 studies were identified and screened. RESULTS: We included a total of 21 publications. The most common histology seen in trials was clear cell carcinoma. A variety of interventions were reviewed including immunotherapy, medroxyprogesterone acetate, interferon alfa, and tyrosine kinase inhibitors. Most trials did not demonstrate a benefit in relapse-free survival (RPS) or overall survival (OS). Pembrolizumab demonstrated a significant difference in disease recurrence in the KEYNOTE-564 trial although median data was not reached. Blinded independent reviewers identified a benefit in disease-free survival (DFS) with Sunitinib in the S-TRAC trial. CONCLUSION: There was not a clear benefit in using adjuvant therapy broadly for resected locoregional RCC; however, further investigation should be done in the highest-risk group to elucidate potential benefit.

Background. Urine leakage from urethrovesical anastomosis (UVA) is a frequent and significant complication after prostatectomy.Aim. To determine frequency urine leakage from the anastomosis after prostatectomy, evaluate diagnostic methods, develop classification and management guidelines for patients with this complication.Materials and methods. A retrospective analysis of 1426 patients who underwent prostatectomy was performed. Results. In total, 97 (6.8 %) patients developed UVA failure in the early postoperative period. The complication was diagnosed on the 7th day after prostatectomy using retrograde cystography. An original classification urine leakage from the anastomosis after prostatectomy was proposed using numbers (0, I, II, III) and letters (A, B, C). In 50 (3.4 %) patients, grade I (A, B, C) UVA failure was diagnosed; 38 (2.7 %) patients had grade II (A, B, C) UVA failure; 9 (0.6 %) patients had grade III (A, B) UVA failure. The developed classification allows to accurately determine the severity of UVA failure and apply the appropriate methods for its correction.Conclusion. Urine leakage from UVA is a serious problem in surgical treatment of prostate cancer. Currently, it is necessary to systematize the available data and introduce unified classification and algorithm for correcting this complication into clinical practice.

Background. Metastatic castration-resistant prostate cancer remains a complex problem due to patients' previous treatments and limited selection of subsequent therapies. While 2nd generation antiandrogens are initially effective, resistance to them is not an exceptional event. Mechanisms depending on androgen receptor and independent of it have been described. A special focus is on mutations in DNA repair genes, particularly genes involved in homologous recombination repair (HRR) as a possible cause of somatic genetic abnormalities specifically in progressive metastatic disease. However, data on the effect of the HRR defect on the effectiveness of antiandrogen therapy for prostate cancer are very limited, which requires additional clinical studies.Aim. To evaluate the effect of clinical, morphological, molecular and genetic factors on the effectiveness of enzalutamide antiandrogen therapy in patients with prostate cancer and known mutations in DNA repair genes involved in HRR and mismatch repair.Materials and methods. The study was performed at the Clinical Oncological Dispensary No. 1 (Krasnodar). Retrospective analysis of clinical and morphological parameters of 54 patients with prostate cancer who received enzalutamide antiandrogen therapy and with known status of germ line and somatic mutations of HRR DNA repair genes (BRCA1, BRCA2, ATM, BARD, BRIP1, CDK12, CHEK1, CHEK2, PALB2, RAD51B, RAD51C, RAD54L, FANCL) and microsatellite instability in immunohistochemical determination of mismatch repair deficit was performed. Statistical analysis was performed using IBM SPSS Statistics v.22 software.Results and conclusion. In 17 of 54 patients, pathogenic germline and somatic mutations of HRR genes were detected: 7 mutations in BRCA2 gene, 4 - in CHEK2, 2 - in BRCA1, 2 - in CDK12, 1 - in BRIP1 and 1 - in ATM. It was shown that in the group of patients with metastatic castration-resistant prostate cancer, histological grade per the International Society of Urological Pathology (ISUP) G2 (total Gleason score 7 (3 + 4)) is significantly associated with the absence of HRR mutation, and grade G3 (total Gleason score 7 (4 + 3)) was associated with HRR mutations (р р р = 0.008) and radiographic progression (HR 5.161; 95 % CI 1.550-17.187; р = 0.008). Progression risk decreased with increased level of PSA decrease 12-16 weeks after enzalutamide therapy start: for PSA decrease >30 % HR 0.150; 95 % CI 0.040-0.570; р = 0.005; for PSA decrease >50 % HR 0.039; 95 % CI 0.006-0.280; р = 0.001; for PSA decrease >90 % HR 0.116; 95 % CI 0.036-0.375; р = 0.000. Presence of HRR mutation, age p >0.05). Kaplan-Meier curves showed a trend towards increased time to development of castration resistance in the group of primary early cancer (Breslow р = 0.06; Tarone-Ware р = 0.062). Subgroup analysis showed that in the cohort of patients with castration-resistant prostate cancer (n = 48), absence of HRR mutation in patients who previously received docetaxel therapy increases time to PSA-progression compared to patients with mutations (log-rank р

In the last ten years, the number of organ preservation surgeries for kidney cancer significantly increased. Per literature data, the incidence of recurrences after partial nephrectomy is between 2.9 and 11 %, mostly they are located in the operated or contralateral kidney. Positive surgical margin, high stage and histological subtype of the tumor, as well as hereditary diseases, can serve as predictors for recurrences. In renal cancer recurrences, radical nephrectomy, ablation therapy and repeat tumor resection are possible treatment methods. Kidney resection, same as in primary renal tumors, leads to chronic kidney disease and cardiovascular complications. Different ablation methods, despite their low invasiveness, are not always technically possible. Therefore, in patients with kidney cancer recurrence and satisfactory functional status, repeat partial nephrectomy can be a method of choice. The literature describes the outcomes of open repeat kidney resection with high incidence of general and severe complications. The number of these complications significantly decreased due to the use of robot-assisted access for resection of recurrent renal tumors. Functional characteristics of repeat kidney resections do not significantly decrease, especially in robot-assisted partial nephrectomy. Oncological outcomes of these surgeries remain intermediate, further prospective multi-center trials are needed for their confirmation.

Renal cell carcinoma is one of the most common malignant neoplasms of the genitourinary system. Along with smoking and hereditary syndromes associated with mutations in the Von Hippel-Lindau (VHL) gene, obesity is one of the main risk factors for the development of renal cell carcinoma. Emerging data indicate a causal relationship between obesity and development of renal cell carcinoma. In a large study within the framework of the Metabolic Syndrome and Cancer project, clinical data on blood pressure, body mass index, blood glucose, cholesterol and triglycerides were collected in 560,388 people. Individually, high glucose and triglyceride levels, as well as high body mass index and blood pressure, correlated with an increased risk of renal cell carcinoma in men, while only body mass index had a significant correlation in women.

Background. Currently, the group of intermediate risk prostate cancer (PC) includes 2 subgroups - favorable and unfavorable intermediate risk according to the National Comprehensive Cancer Network (NCCN) classification. The optimal scope of therapy is not defined for the unfavorable intermediate risk subgroup. In particular, the need for and duration of hormone therapy (HT) during combined radiotherapy (CRT) have not yet been determined.Aim. To perform a comparative analysis of the efficacy and toxicity of CRT in patients with unfavorable intermediate risk treated with and without HT.Materials and methods. Eighty-four (84) patients with unfavorable intermediate risk PC were treated with CRT at the clinic of the A.F. Tsyb Medical Radiological Research Center between May 2016 and December 2020. Patients were divided into two groups: external beam radiation therapy + brachytherapy (n = 40) and external beam radiation therapy + brachytherapy + HT (n = 44). Conformal external beam radiation therapy was delivered with conventional fractionation to a total dose of 44-46 Gy and the 192Ir high-dose rate brachytherapy was delivered with a single fraction of 15 Gy. Median duration of HT consisting of gonadotropin-releasing hormone agonist was 6 months. Median age was 65.2 years (range: 49-80 years). Median follow-up was 58.1 months (range: 18.6-83.7 months).Results. With a median follow-up of 4.8 years, progression-free survival was 95 % and 97.6 % in the external beam radiation therapy + brachytherapy group and external beam radiation therapy + brachytherapy + HT group, respectively (p = 0.578). The break between treatment stages of more than 28 days was associated with a statistically significant increase in the risk of PC recurrence (p = 0.007). Overall survival for the external beam radiation therapy + brachytherapy group versus external beam radiation therapy + brachytherapy + HT group was 97.5 and 93.2 % (p = 0.376), respectively.Late genitourinary toxicity was grade I in 8 (9.5 %) patients and grade II in 1 (1.2 %) patient. Urethral stricture developed in 3 (3.6 %) patients. Late gastrointestinal toxicity was grade I in 7 (8.3 %) patients and grade II in 1 (1.2 %) patient. There were no statistically significant differences in the incidence of late complications between groups with and without HT. There was a statistically significant (p = 0.049) effect of prostate volume on the incidence of late radiation proctitis.Conclusion. There were no statistically significant differences in progression-free survival and overall survival in patients with unfavorable intermediate risk PC who received external beam radiation therapy + brachytherapy with or without HT. The incidence and severity of adverse events were acceptable and allowed patients with PC to maintain high quality of life.

Background. Prostate cancer (PCa) is the 2nd most common oncological disease among men in the world. The first structured program of robot-assisted radical prostatectomy (RARP) was started in the year 2000. In the medical literature, a limited number of studies on long-term oncological treatment outcomes for patients with PCa after RARP is presented. In Russia, the Da Vinci robot was first installed in 2007. In the Urology Clinic of the A.I. Evdokimov Moscow State University of Medicine and Dentistry, the program of robot-assisted surgery was started in November of 2008.Aim. To perform first in Russia evaluation of 10-year oncological treatment outcomes for patients with localized PCa after RARP. To perform comparative analysis with the outcomes of radical retropubic prostatectomy (RRP).Materials and methods. Retrospective analysis of medical histories of 211 patients was performed. Among them, 62 patients did not satisfy the inclusion criteria. The remaining 149 patients were divided into 2 groups: 1st - RARP (n = 82), 2nd - RRP (n = 67). All RARP were performed by the same surgeon, RRP by 2 experienced surgeons.Results. Median follow-up was 110.35 ± 24.58 and 115.19 ± 15.37 months in the 1st and 2nd group, respectively; median follow-up was 120 months in both groups (p >0.05). Survival was calculated using the Kaplan-Meyer approach. Ten-year biochemical recurrence (BCR)-free survival was 79.3 and 82.1 %, clinical recurrence-free survival was 96.3 and 97.1 %, metastasis-free survival was 92.7 and 94.0 %, cancer-specific survival was 93.9 and 95.6 % and overall survival was 85.4 and 86.6 % in the 1st and 2nd group, respectively. Mean time to BCR was 17.00 ± 20.67 and 22.83 ± 26.51 months, respectively ( p >0.05). Calculation of BCR predictors was performed using correlation analysis based on contingency test and Cramer's V-test. In the 1st group, body mass index ≥30 kg/m2 (p = 0.01), prostate-specific antigen level >10 ng/mL (p = 0.04), high progression risk per the D'Amico classification (p = 0.01) were independent preoperative predictors of BCR. Gleason score 7 (4 + 3) (p = 0.04) and ≥8 (p p Conclusion. RARP demonstrates long-term (10-year) oncological effectiveness comparable to oncological effectiveness of RRP in patients with localized PCa.

Survival rates for cancer patients continue to steadily increase due to improvement of effectiveness of current treatments. However, despite significant oncological results, one should not forget about the quality of life of this cohort of patients, in particular those who undergo gonadotoxic cancer therapy with development of premature ovarian failure in women and azoospermia in men. Preservation of fertility in both women and men with cancer is currently possible and should be integrated at all levels of cancer care. In this regard, the main purpose of this review is to consider the topic of fertility in men treated for cancer in the context of various aspects of human life.

Background. Renal cell carcinoma is one of the most common urologic cancers. Due to development of modern diagnostic methods, kidney tumors are often diagnosed at early stages (cT1a-T1b). The golden standard of treatment of localized renal cell carcinoma is tumor resection. In retroperitoneoscopic access, the time to artery access is decreased, the risk of intra- and postoperative complications is reduced. Retroperitoneal access is preferable for tumors located on the lateral or posterior kidney surface.Aim. To analyze the results of treatment of patients after retroperitoneoscopic kidney resection.Materials and methods. Between 2018 and 2021, at the A.F. Tsyb Medical Radiological Research Center - branch of the National Medical Research Radiological Center 47 retroperitoneoscopic kidney resections were performed (29 (61.7 %) in men, 18 (38.3 %) in women) due to stage cT1aN0M0 renal cell carcinoma. Retrospective analysis of demographic data, comorbid status, tumor characteristics, operative time, blood loss volume, frequency and severity of complications per the Clavien-Dindo classification was performed. Complexity of resection was evaluated using the R.E.N.A.L. scale.Results. Mean patient age was 63 (38-79) years, body mass index was 29.9 (22-39) kg/m2. Tumor of the left kidney was diagnosed in 24 (51.0 %) cases, of the right kidney - in 22 (46.8 %) cases, bilateral lesions - in 1 (2.2 %) case. Mean tumor size was 22.4 (11-39) mm. Resection had low complexity in 35 (74.5 %) cases, intermediate complexity in 12 (25.5 %) cases. Mean operative time was 156 (80-280) minutes, mean warm ischemia time was 19 (7-32) minutes, number of resections with zero ischemia was 15 (31.9 %), mean blood loss volume was 53 (10-300) mL, number of resections without renal parenchyma suturing was 10 (21.3 %). Mean hospitalization time after surgery was 5 days. Postoperative complications were observed in 4 (8.5 %) cases: bleeding (severity grade II per the Clavien-Dindo classification) in 1 (2.1 %) case, postoperative infectious complications (severity grade II) - in 2 (4.2 %) cases, subcutaneous hematoma (severity grade I) - in 1 (2.1 %) case.Conclusion. Retroperitoneoscopic access is effective and safe. This is confirmed by low frequency and severity of postoperative complications. This access allows to reduce hospitalization time and pain management medication which accelerates patient mobilization and recovery. Comparative analysis shows that retroperitoneoscopic kidney resection has the same effectiveness as laparoscopic resection.

We present the largest testicular tumour that first ever reported in Malaysia and we believed first reported in Southeast Asia. A 21 years old Malay gentleman presented to us with painless large scrotal swelling. After the initial workup and investigations were done and followed by a CT scan which yield a multiple paraaortic lymph nodes, the patient was scheduled listed in the earliest list for high ligation right orchidectomy with an inguinal approach. The patient seeks treatment at that point because he can't bear the embarrassment and fear of the treatment.

28 сентября 2022 г. в Санкт-Петербурге состоялся Совет экспертов, на котором ведущими онкоурологами страны обсуждались вопросы лечения пациентов с метастатическим гормоночувствительным раком предстательной железы, профиль пациентов для назначения тройной комбинации и современные возможности терапии.

Background. In recent years, an increase in the incidence of multiple primary malignancies has been observed. Multiple primary malignancies are an independent occurrence and development of two or more neoplasms of different histological origin in one patient.Aim. To evaluate epidemiological, clinical and morphological aspects of primary multiple malignant neoplasms of the prostate, kidney, and bladder.Materials and methods. Data analysis of the work report of the Saratov region oncological service in 2019, presented by the Regional Clinical Oncological Dispensary, patient case histories in the archive of the medical information system was performed.We performed a comparative analysis of the literature sources and data we obtained based to the following criteria: topographic anatomical combination of tumor locations, distribution of tumor combinations depending on time of occurrence (synchronous, metachronous), dynamics of urogenital multiple primary malignancies diagnosis in 2012-2019, distribution by gender and age, combination of stages of tumor process in both tumors, distribution by combination of histological types.Results. Between 2012 and 2019, 783 cases of multiple primary tumors with lesions in the urogenital system were identified. We studied 186 cases with a combination of two malignant neoplasms in the prostate, kidney, and bladder. Tumors developed synchronously in 36 % of patients, metachronously in 64 %. Mean patient age was 75 years. Half of the cases were in the group of localized stages - 90 (48.4 %), with the most common combination of TI-TII stages observed in 46 (24.7 %) cases. Combinations of acinar adenocarcinoma of the prostate with urothelial carcinoma of the bladder (34.7 %), clear cell renal carcinoma (27.8 %), papillary urothelial carcinoma of the bladder (12.5 %) were the most common according to histological diagnosis of primary multiple tumors of the urogenital system.Conclusion. Over the recent years we can observe a steady growth of diagnosable urogenital multiple primary malignancies. Morphological verification of the tumor and revelation of the most frequent histological types allows to assume the presence of the common mechanisms of development and the influence of tumor microenvironment on the growth of both tumors in a multiple primary malignancies pair.

Background. Ionizing radiation is an effective antitumor therapy, but it has a serious negative effect on the immune system requiring the use of radiation reaction prevention and reduction methods. Neutrophils are a sensitive element of the immune system both in interaction with tumor tissue and in response to radiation injury.Aim. To evaluate functional activity of peripheral blood neutrophils by chemiluminescent analysis in patients with anorectal cancer after radiotherapy.Materials and methods. The study included 80 patients with anorectal cancer. Patients received chemo- and radio-therapy with 3D conformal radiotherapy and radiation therapy under visual control, followed by the use of radioprotector and without it. Neutrophil activity determined by chemiluminescent analysis.Results. In patients with anorectal cancer found maximum spontaneous and induced chemiluminescence acceleration. The chemiluminescence activation index with luminol is lower in patients with anorectal cancer, and with lucigenin shows no differences with the control group. The low luminol chemiluminescence maximum intensity, as well as the decrease in the synthesis of reactive secondary oxygen species in enzymatic systems, is likely regulatory intracellular limitations consequence. After treatment, patients with radioprotector showed a decrease in the number of parameters with statistically significant differences with the control group. Undesirable phenomena associated with sodium deoxyribonucleate therapy not detected in anorectal cancer patients during radiotherapy and subsequent observation period.Conclusion. During treatment, differences in chemiluminescence parameters suggest that ionizing radiation affects them in patients with anorectal cancer receiving standard chemoradiotherapy. Use of chemoradiotherapy with a radioprotector leads to indirect restoration of cellular functional activity. This is confirmed by luminol-dependent chemiluminescence faster reaching its maximum and a decrease in the number of significant differences from the control group after the start of the drug treatment.

Purpose: an assessment of efficacy and safety of cabozantinib in unselected patients with metastatic renal cell carcinoma in the first and subsequent lines of therapy.Materials and methods. Russian multicenter observational study included 92 consecutive patients with morphologically verified metastatic renal cell carcinoma treated with cabozantinib (60 mg/d) in 16 Russian centers. Median age of the patients was 56 (19-79) years, a male-to-female ratio - 3:1. At the start of cabozantinib therapy 27.2 % of patients had ECOG PS 2. Most common histological type of kidney cancer was clear-cell RCC (90.2 %). Most patients were diagnosed with synchronous (71.7 %) multiple metastases (60.9 %). Previous nephrectomy was performed in 87.0 % of cases. Prognosis according to International Metastatic Renal Cancer Database Consortium (IMDC) score was assessed as favorable in 5.4 %, intermediate - in 58.7 % and poor - in 35.9 % patients. Cabozantinib as the first-line therapy was administered in 9 (9.8 %), following 1-5 lines of systemic treatment - in 83 (90.2 %) cases. Median follow-up was 11 (2.3-44.5) months.Results. In patients, receiving cabozantinib as the first-line therapy, objective response rate was 66.7 %, tumor control was reached in 100 % of cases. Median time to the objective response was 2.6 (1.9-3.6) months, median objective response duration - 13.2 (6.2-21.5) months. Median progression-free survival (PFS) and overall survival (OS) were not reached, 6- and 12-months PFS was 77.8 % and 77.8 %, 6- and 12-months OS - 88.9 % and 88.9 % respectively. Cabozantinib as the second and subsequent lines of therapy provided objective response rate of 34.9 %, tumor control rate - 97.6 %. Median time to the objective response was 2.5 (1.8-4.1) months, median objective response duration - 12.6 (5.5-27.3) months. Median PFS was not reached (6- and 12-months PFS - 92.5 % and 73.1 % respectively), median OS was 32.6 months (6- and 12-months OS - 97.4 % and 80.8 % respectively). Any adverse events (AE) developed in 88.8 %, AE grade III-IV - in 32.6 % of cases. Most frequent AE grade III-IV included arterial hypertension (18.5 %), diarrhea (6.5 %) and palmar-plantar erythrodysesthesia (6.5 %). Unacceptable toxicity demanded treatment cancellation in 2.2 %, therapy interruption - in 16.3 % and dose reduction - in 30.4 % of patients.Conclusion. Cabozantinib as the first and subsequent lines of therapy for metastatic renal cell carcinoma patients in the real world practice demonstrated high efficacy and better tolerability comparing with population assigned for cabozantinib monotherapy in the randomized phase II-III trials.

Background. Bladder cancer, or urothelial carcinoma, is a common, aggressive, and still difficult to predict disease. For adequate therapy, timely diagnosis is essential since early detection of this tumor can significantly increase patient's survival at any age. Molecular genetic studies in cancer patients, including those with urothelial carcinoma, are becoming increasingly important. A number of major molecular genetic biomarkers of urothelial carcinoma are described in the world literature and used in clinical practice, however, information on the role of microRNA (miRNA) studies in the diagnosis of this disease has become available only in recent years.Aim. To examine information of the world literature on the significance of miRNA identification in resected bladder tissues with non-muscle invasive urothelial tumors.Materials and methods. We studied information from the world medical literature in the PubMed, CrossRef and Scopus databases dated between 2001 and 2022 on the significance of miRNA identification in resected bladder tissues with non-muscle invasive urothelial tumors.Results. The results of the studies demonstrate that predictive levels of some miRNAs, as well as their associated proteins, should be assessed in the original tumor tissue and urinary vesicles in different clinical settings. The use of molecular genetic research, as one of the new diagnostic methods, will allow to personalize treatment for a particular patient and, if necessary, make a choice in favor of a more aggressive treatment method. In turn, this will increase the overall survival and quality of life of patients with aggressive tumors.Conclusion. The next few years may bring many new discoveries that will help to unlock the secrets of miRNA dysregulation in urothelial carcinoma, leading to development and application of new targeted therapies in this patient population.