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Elena S Kotova,1 Yulia A Savochkina,2 Yuriy V Doludin,3 Alexander O Vasilyev,4 Elena A Prilepskay,4 Natalia V Potoldykova,3 Konstantin A Babalyan,1 Alexandra V Kanygina,1 Andrey O Morozov,3 Alexander V Govorov,4 Dmitry V Enikeev,3 Elena S Kostryukova,1 Elena N Ilina,1 Vadim M Govorun,1 Dmitry Y Pushkar,4 Elena I Sharova1 1Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia; 2Lytech Ltd, Moscow, Russia; 3Sechenov First Moscow State Medical University, Moscow, Russia; 4Department of Urology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, RussiaCorrespondence:Elena S KotovaDepartment of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Malaya Pirogovskaya 1a, Moscow 119992, RussiaTel +7 910 464 56 55Fax +7 499 246 44 09Email potamanthus@gmail.comPurpose: Preclinical evaluation of PCA3 and AMACR transcript simultaneous detection in urine to diagnose clinical significant prostate cancer (prostate cancer with Gleason score ≥ 7) in a Russian cohort.Patients and Methods: We analyzed urine samples of patients with a total serum PSA ≥ 2 ng/mL: 31 men with prostate cancer scheduled for radical prostatectomy, 128 men scheduled for first diagnostic biopsy (prebiopsy cohort). PCA3, AMACR, PSA and GPI transcripts were detected by multiplex reverse transcription quantitative polymerase chain reaction, and the results were used for scores for calculation and statistical analysis.Results: There was no significant difference between clinically significant and nonsignificant prostate cancer PCA3 scores. However, there was a significant difference in the AMACR score (patients scheduled for radical prostatectomy p=0.0088, prebiopsy cohort p=0.029). We estimated AUCs, optimal cutoffs, sensitivities and specificities for PCa and csPCa detection in the prebiopsy cohort by tPSA, PCA3 score, PCPT Risk Calculator and classification models based on tPSA, PCA3 score and AMACR score. In the clinically significant prostate cancer ROC analysis, the PCA3 score AUC was 0.632 (95%CI: 0.511– 0.752), the AMACR score AUC was 0.711 (95%CI: 0.617– 0.806) and AUC of classification model based on the PCA3 score, the AMACR score and total PSA was 0.72 (95%CI: 0.58– 0.83). In addition, the correlation of the AMACR score with the ratio of total RNA and RNA of prostate cells in urine was shown (tau=0.347, p=6.542e– 09). Significant amounts of nonprostate RNA in urine may be a limitation for the AMACR score use.Conclusion: The AMACR score is a good predictor of clinically significant prostate cancer. Significant amounts of nonprostate RNA in urine may be a limitation for the AMACR score use. Evaluation of the AMACR score and classification models based on it for clinically significant prostate cancer detection with larger samples and a follow-up analysis is promising.Keywords: prostatic neoplasms, early diagnosis, neoplasm grading, alpha-methylacyl-CoA racemase, RNA

Prostate cancer (PC) is one of the major causes of death among elderly men. PC is often diagnosed later in progression due to asymptomatic early stages. Early detection of PC is thus crucial for effective PC treatment. The aim of this study is the simultaneous highly sensitive detection of a palette of PC-associated microRNAs (miRNAs) in human plasma samples. With this aim, a nanoribbon biosensor system based on "silicon-on-insulator" structures (SOI-NR biosensor) has been employed. In order to provide biospecific detection of the target miRNAs, the surface of individual nanoribbons has been sensitized with DNA oligonucleotide probes (oDNA probes) complementary to the target miRNAs. The lowest concentration of nucleic acids, detectable with our biosensor, has been found to be 1.1 × 10 -17 M. The successful detection of target miRNAs, isolated from real plasma samples of PC patients, has also been demonstrated. We believe that the development of highly sensitive nanotechnology-based biosensors for the detection of PC markers is a step towards personalized medicine.

The aim of this study was to determine the influence of high-intensity training under extreme conditions (T = 40 °C) on the metabolism and immunological reactions of athletes. Male triathletes ( n = 11) with a high level of sports training performed load testing to failure (17 ± 2.7 min) and maximum oxygen consumption (64.1 ± 6.4 mL/min/kg). Blood plasma samples were collected before and immediately after exercise. Mass spectrometric metabolomic analysis identified 30 metabolites and 6 hormones in the plasma, of which 21 and 4 changed after exercise, respectively. Changes in the intermediate products of tricarboxylic and amino acids were observed (FC > 1.5) after exercise. The obtained data can be associated with the effect of physical activity on metabolism in athletes. Therefore, constant monitoring of the biochemical parameters of athletes can help coaches identify individual shortcomings in a timely manner and track changes, especially as the volume of training increases. In addition, it was revealed that the immunological reaction (manifestation of a hyperactive reaction to food components) is personalized in nature. Therefore, it is important for coaches and sports doctors to analyze and control the eating behavior of athletes to identify food intolerances or food allergies in a timely manner and develop an individual elimination diet.

A novel HPLC-ESI-MS/MS method for simultaneous gonadotropin-releasing hormone (GnRH) analogs and somatostatin analog quantitation was developed and validated. The developed method was successfully applied to pharmacokinetic studies. The sample preparation process included solid-phase extraction (SPE). Effective chromatographic separation of the analytes and internal standard (dalargin) was achieved with a C18 column, using a gradient elution with two mobile phases: 0.1% v / v formic acid (aqueous solution) and 0.1% v / v formic acid (acetonitrile solution). The linearity of the method was demonstrated within a concentration range of 0.5-20 ng/mL, with correlation coefficients between 0.998-0.999 for goserelin, buserelin, triptorelin, and octreotide, respectively. The relative standard deviation (RSD, %) values for method accuracy and precision did not exceed 20% at the lower level of quantitation (LLOQ) or 15% at other concentration levels.

Introduction: According to the recommendations of the European Association of Urology the presence of a suspicious lesion on MRI is an indication for both primary and secondary MR-targeted biopsies. At the same time, the Russian Society of Urologists recommends to perform mpMR/US fusion biopsy only in patients with a prior negative biopsy. In clinical practice, mpMR/US fusion and cognitive biopsies are the most frequently performed. However, when comparing them, contradictory data on detection of clinically significant prostate cancer is obtained., Objective: to compare the detection rate of clinically significant prostate cancer performing cognitive and mpMR/US fusion biopsies., Materials and Methods: Inclusion criteria: PSA >2 ng/mL and/or a positive DRE, and/or a suspicious lesion on TRUS, and PI-RADSv2.1 lesion more or equal 3. At first, "unblinded" urologist performed a transperineal mpMR/ultrasound fusion and saturation biopsy. Then "blinded" urologist obtained transrectal cognitive biopsy Clinically significant cancer was defined as ISUP more or equal 2., Results: We enrolled 96 patients. Median age was 63 years, prostate volume - 47 cm3 and PSA - 6.82 ng/mL. MpMR/US fusion and cognitive biopsies were comparable in regard to the detection rate of clinically significant (32.3% vs 25.0%; p=0.264), clinically insignificant cancer (25.0% and 26.0%; p=0.869) and overall detection rate (57.3% and 51%;p=0.385). Both biopsies missed clinically significant cancer with equal frequency (5.2%; p=0.839). Histological efficacy also was comparable. The number of positive cores between mpMR/US fusion and cognitive biopsy was equal (34.1% and 31.1% respectively; p= 0.415). At the same time, no statistically significant difference was found with respect to maximum cancer core length (53.1% vs 47.7%, respectively; p=0.293)., Conclusion: The results suggest that both cognitive and mpMR/US fusion biopsies are equally accurate diagnostic methods for clinically significant prostate cancer detection, thus their wider introduction into clinical practice is necessary.

Prostate cancer (PCa) diagnosis is primarily based on prostate-specific antigen (PSA) testing and prostate tissue biopsies. However, PSA testing has relatively low specificity, while tissue biopsies are highly invasive and have relatively low sensitivity at early stages of PCa. As an alternative, we developed a technique of liquid biopsy, based on isolation of circulating tumor cells (CTCs) from seminal fluid (SF). The recovery of PCa cells from SF was demonstrated using PCa cell lines, achieving an efficiency and throughput as high as 89% (±3.8%) and 1.7 mL min -1 , respectively, while 99% (±0.7%) of sperm cells were disposed of. The introduced approach was further tested in a clinical setting by collecting and processing SF samples of PCa patients. The yield of isolated CTCs measured as high as 613 cells per SF sample in comparison with that of 6 cells from SF of healthy donors, holding significant promise for PCa diagnosis. The correlation analysis of the isolated CTC numbers with the standard prognostic parameters such as Gleason score and PSA serum level showed correlation coefficient values at 0.40 and 0.73, respectively. Taken together, our results show promise in the developed liquid biopsy technique to augment the existing diagnosis and prognosis of PCa.

Aim: To evaluate the efficiency of radio wave electrotherapy (448 kHz) for the treatment of patients with organic erectile dysfunction (ED)., Materials and Methods: A prospective, randomized, blind, sham- controlled clinical trial was carried out. Inclusion criteria were as following: 1) patients with 5 to 20 points on the IIEF-5 score; 2) patients with proven organic erectile dysfunction lasting at least 6 months; 3) patients with penile arterial insufficiency and/or venous insufficiency, confirmed by doppler study of penile vessels with pharmacological stimulation (peak systolic velocity (PSV) <25 cm/s, end-diastolic blood flow velocity (DPV) >5 cm/s, resistance index (IR) < 0.8). The participants were randomized into two groups (experimental and control) in a 1:1 ratio. The full treatment course lasted 9 weeks. Patients underwent an assessment of erectile function based on questionnaires (IIEF-5, SEP, Schramek), as well as Doppler ultrasound of the cavernous arteries before inclusion in the study as well as a after treatment., Results: The study included 61 men (experimental group [n=31], control group [n=30]. There was a significant difference in the IIEF-5 scores after treatment between the experimental group and the control group (19.5+/-3.2 vs. 15.1+/-5.4, p=0.017, respectively). Significant differences were also noted in mean total score of the SEP questionnaire: an increase to 3.6+/-1.0 in the treatment group compared to 2.4+/-1.1 in the control group (p=0.004). The results of the Schramek questionnaire also demonstrated a significant increase in the mean score in the experimental group compared to the control group: 4.2+/-0.6 vs. 3.2+/-1.0 (p=0.011). The response time to the drug and the detumescence time also significantly differed between the two groups: 11.9+/-4.0 min vs. 15.5+/-4.1 min, p=0.001 and 126.6+/-60.7 min vs. 66.2+/-40.9, p<0.001, respectively. Neither complications nor any adverse events were recorded during treatment or after its completion., Conclusions: Radio wave electrotherapy with a radiofrequency of 448 kHz can improve the IIEF-5, SEP and Schramek scores, as well as the indicators of ultrasound Doppler ultrasonography in patients with organic ED. To assess the feasibility of this method in patients with organic ED of different stages, further studies are needed.

Context: Degarelix is associated with high rates of injection site reaction. The US Food and Drug Administration approved relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, for the treatment of advanced prostate cancer patients., Objective: This systematic review and network meta-analysis aimed to compare the efficacy and safety of relugolix versus degarelix., Evidence Acquisition: A systematic search was performed using major web databases for studies published before January 30, 2021, according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) extension statement for a network meta-analysis. Studies that compared the efficacy (12-mo castration rate with testosterone ≤50 ng/dl) and safety (adverse events [AEs]) of relugolix or degarelix and of the control group (GnRH agonists) were included. We used the Bayesian approach in the network meta-analysis., Evidence Synthesis: Four studies (n = 2059) met our eligibility criteria. The main efficacy analysis was conducted for two different treatments (relugolix and all doses of degarelix vs GnRH agonists); relugolix (risk ratio [RR] 1.09, 95% credible interval [CrI]: 0.95-1.23) and degarelix (RR 0.98, 95% CrI: 0.91-1.06) were not associated with different 12-mo castration rates. In the subgroup analysis, degarelix 480 mg was significantly associated with a lower castration rate (RR 0.46, 95% CrI: 0.07-0.92). In all efficacy ranking analyses, relugolix achieved the best rank. The safety analyses showed that relugolix (RR 0.99, 95% CrI: 0.6-1.6 and RR 0.72, 95% CrI: 0.4-1.3, respectively) and degarelix (RR 1.1, 95% CrI: 0.75-1.35 and RR 1.05, 95% CrI: 0.42-2.6, respectively) were not associated with either all AE or serious AE rates. In the ranking analyses, degarelix achieved the worst rank of all AEs and the best rank of serious AEs. Relugolix (RR 0.44, 95% CrI: 0.16-1.2) and degarelix (RR 0.74, 95% CrI: 0.37-1.52) were not associated with different cardiovascular event (CVE) rates; both were associated with lower CVE rates than GnRH agonists in the ranking analyses., Conclusions: We found that the efficacy and safety of relugolix are comparable with those of degarelix, albeit with no injection site reaction. Such data should be interpreted with caution until large-scale direct comparison studies with a longer follow-up are available., Patient Summary: We found that relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, has comparable efficacy and safety with degarelix, a parenteral GnRH antagonist, for the treatment of advanced prostate cancer patients., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: This study aimed to evaluate the concordance in tumor stage and grade between ureteroscopic (URS) biopsy and radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC)., Patients and Methods: Records of 1,214 UTUC patients who had undergone URS biopsy followed by RNU were included. Univariable and multivariable logistic regression analyses were performed to identify factors contributing to the pathological upstaging., Results: The concordance between URS biopsy-based clinical and RNU pathological staging was 34.5%. Clinical understaging occurred in 59.5% patients. Upstaging to muscle-invasive disease occurred in 240 (41.7%) of 575 patients diagnosed with ≤cT1 disease. Of those diagnosed with muscle-invasive disease on final pathology, 89.6% had been clinically diagnosed with ≤cT1 disease. In the univariable analyses, computed tomography urography (CTU)-based invasion, ureter location, hydronephrosis, high-grade cytology, high-grade biopsy, sessile architecture, age, and women sex were significantly associated with pathological upstaging (P < .05). In the multivariable analyses, CTU-based invasion and hydronephrosis remained associated with pathological upstaging (P < .05). URS biopsy-based clinical and pathological gradings were concordant in 634 (54.2%) patients. Clinical undergrading occurred in 496 (42.4%) patients., Conclusions: Clinical understaging/undergrading and upstaging to muscle-invasive disease occurred in a high proportion of UTUC patients undergoing RNU. Despite the inherent selection bias, these data underline the challenges of accurate UTUC staging and grading. In daily clinical practice, URS biopsy and CTU offer the most accurate preoperative information albeit with limited predictive value when used alone. These findings should be considered when utilizing preoperative, risk-adapted strategies., (Copyright © 2021. Published by Elsevier Inc.)

A nanoribbon biosensor (NRBS) was developed to register synthetic DNAs that simulate and are analogous to miRNA-17-3p associated with colorectal cancer. Using this nanoribbon biosensor, the ability to detect miRNA-17-3p in the blood plasma of a patient diagnosed with colorectal cancer has been demonstrated. The sensing element of the NRBS was a nanochip based on a silicon-on-insulator (SOI) nanostructure. The nanochip included an array of 10 nanoribbons and was designed with the implementation of top-down technology. For biospecific recognition of miRNA-17-3p, the nanochip was modified with DNA probes specific for miRNA-17-3p. The performance of the nanochip was preliminarily tested on model DNA oligonucleotides, which are synthetic analogues of miRNA-17-3p, and a detection limit of ~10 -17 M was achieved. The results of this work can be used in the development of serological diagnostic systems for early detection of colorectal cancer.

The association between cancer risk and schizophrenia is widely debated. Despite many epidemiological studies, there is still no strong evidence regarding the molecular basis for the comorbidity between these two pathological conditions. The vast majority of assays have been performed using clinical records of schizophrenic patients or those undergoing cancer treatment and monitored for sufficient time to find shared features between the considered conditions. We performed mass spectrometry-based proteomic and metabolomic investigations of patients with different cancer phenotypes (breast, ovarian, renal, and prostate) and patients with schizophrenia. The resulting vast quantity of proteomic and metabolomic data were then processed using systems biology and one-dimensional (1D) convolutional neural network (1DCNN) machine learning approaches. Traditional systematic approaches permit the segregation of schizophrenia and cancer phenotypes on the level of biological processes, while 1DCNN recognized "signatures" that could segregate distinct cancer phenotypes and schizophrenia at the comorbidity level. The designed network efficiently discriminated unrelated pathologies with a model accuracy of 0.90 and different subtypes of oncophenotypes with an accuracy of 0.94. The proposed strategy integrates systematic analysis of identified compounds and application of 1DCNN model for unidentified ones to reveal the similarity between distinct phenotypes., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the prognostic role of the preoperative systemic immune-inflammation index (SII) in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU)., Materials and Methods: We retrospectively analyzed our multi-institutional database to identify 2492 patients. SII was calculated as platelet count × neutrophil/lymphocyte count and evaluated at a cutoff of 485. Logistic regression analyses were performed to investigate the association of SII with muscle-invasive and non-organ-confined (NOC) disease. Cox regression analyses were performed to investigate the association of SII with recurrence-free, cancer-specific, and overall survival (RFS/CSS/OS)., Results: Overall, 986 (41.6%) patients had an SII > 485. On univariable logistic regression analyses, SII > 485 was associated with a higher risk of muscle-invasive (P = 0.004) and NOC (P = 0.03) disease at RNU. On multivariable logistic regression, SII remained independently associated with muscle-invasive disease (P = 0.01). On univariable Cox regression analyses, SII > 485 was associated with shorter RFS (P = 0.002), CSS (P = 0.002) and OS (P = 0.004). On multivariable Cox regression analyses SII remained independently associated with survival outcomes (all P < 0.05). Addition of SII to the multivariable models improved their discrimination of the models for predicting muscle-invasive disease (P = 0.02). However, all area under the curve and C-indexes increased by < 0.02 and it did not improve net benefit on decision curve analysis., Conclusions: Preoperative altered SII is significantly associated with higher pathologic stages and worse survival outcomes in patients treated with RNU for UTUC. However, the SII appears to have relatively limited incremental additive value in clinical use. Further study of SII in prognosticating UTUC is warranted before routine use in clinical algorithms., (© 2021. The Author(s).)

Purpose: To evaluate the potential predictive value of the preoperative serum albumin to globulin ratio (AGR) for oncological outcomes in patients treated with radical prostatectomy (RP) for clinically non-metastatic prostate cancer (PCa)., Methods: Pre-operative AGR was assessed in a multi-institutional cohort of 6041 patients treated with RP. Logistic regression analyses were performed to assess the association of the AGR with advanced disease. We performed Cox regression analyses to determine the relationship between AGR and biochemical recurrence (BCR)., Results: The optimal cut-off value was determined to be 1.31 according to receiver operating curve analysis. Compared to patients with a higher AGR, those with a lower preoperative AGR had worse BCR-free survival (P < 0.01) in the Kaplan-Meier analysis. Pre- and post-operative multivariable models that adjusted for the effects of established clinicopathologic features, confirmed its independent association with BCR [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.31-1.75, P < 0.01, HR 1.55, 95% CI 1.34-1.79, P < 0.01, respectively]. However, the addition of AGR to established prognostic models did not improve their discrimination., Conclusion: While AGR is significantly associated with BCR, in the present study, the clinical impact of AGR was not large enough to affect patient management. Longer follow-up is necessary to observe the true effect of AGR., (© 2021. The Author(s).)

Nanoribbon chips, based on "silicon-on-insulator" structures (SOI-NR chips), have been fabricated. These SOI-NR chips, whose surface was sensitized with covalently immobilized oligonucleotide molecular probes (oDNA probes), have been employed for the nanoribbon biosensor-based detection of a circular ribonucleic acid (circRNA) molecular marker of glioma in humans. The nucleotide sequence of the oDNA probes was complimentary to the sequence of the target oDNA. The latter represents a synthetic analogue of a glioma marker-NFIX circular RNA. In this way, the detection of target oDNA molecules in a pure buffer has been performed. The lowest concentration of the target biomolecules, detectable in our experiments, was of the order of ~10 -17 M. The SOI-NR sensor chips proposed herein have allowed us to reveal an elevated level of the NFIX circular RNA in the blood of a glioma patient.

Objective: To assess the value of preoperative albumin to globulin ratio for predicting pathologic and oncological outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy in a large multi-institutional cohort., Materials and Methods: Preoperative albumin to globulin ratio was assessed in a multi-institutional cohort of 2492 patients. Logistic regression analyses were performed to assess the association of the albumin to globulin ratio with pathologic features. Cox proportional hazards regression models were performed for survival endpoints., Results: The optimal cut-off value was determined to be 1.4 according to a receiver operating curve analysis. Lower albumin to globulin ratios were observed in 797 patients (33.6%) compared with other patients. In a preoperative model, low preoperative albumin to globulin ratio was independently associated with nonorgan-confined diseases (odds ratio 1.32, P = 0.002). Patients with low albumin to globulin ratios had worse recurrence-free survival (P < 0.001), cancer-specific survival (P = 0.001) and overall survival (P = 0.020) in univariable and multivariable analyses after adjusting for the effect of standard preoperative prognostic factors (recurrence-free survival: hazard ratio (HR) 1.31, P = 0.001; cancer-specific survival: HR 1.31, P = 0.002 and overall survival: HR 1.18, P = 0.024)., Conclusions: Lower preoperative albumin to globulin ratio is associated with locally advanced disease and worse clinical outcomes in patients treated with radical nephroureterectomy for upper tract urothelial carcinoma. As it is difficult to stage disease entity, low preoperative serum albumin to globulin ratio may help identify those most likely to benefit from intensified care, such as perioperative systemic therapy, and the extent and type of surgery., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The application of micro-Raman spectroscopy was used for characterization of structural features of the high-k stack (h-k) layer of "silicon-on-insulator" (SOI) nanowire (NW) chip (h-k-SOI-NW chip), including Al 2 O 3 and HfO 2 in various combinations after heat treatment from 425 to 1000 °C. After that, the NW structures h-k-SOI-NW chip was created using gas plasma etching optical lithography. The stability of the signals from the monocrine phase of HfO 2 was shown. Significant differences were found in the elastic stresses of the silicon layers for very thick (>200 nm) Al 2 O 3 layers. In the UV spectra of SOI layers of a silicon substrate with HfO 2 , shoulders in the Raman spectrum were observed at 480-490 cm -1 of single-phonon scattering. The h-k-SOI-NW chip created in this way has been used for the detection of DNA-oligonucleotide sequences (oDNA), that became a synthetic analog of circular RNA-circ-SHKBP1 associated with the development of glioma at a concentration of 1.1 × 10 -16 M. The possibility of using such h-k-SOI NW chips for the detection of circ-SHKBP1 in blood plasma of patients diagnosed with neoplasm of uncertain nature of the brain and central nervous system was shown.

Objectives: To evaluate recurrence and progression risk after simultaneous endoscopic surgery of bladder cancer and benign prostatic hyperplasia (BPH), as simultaneous surgery is not an unusual scenario and theoretically simultaneous transurethral resection of bladder tumour (TURBT) and transurethral resection of the prostate (TURP) can lead to an increased risk of recurrence in the bladder neck and prostatic urethra (BN/PU)., Methods: We conducted a systematic review and meta-analysis to assess the risk of recurrence (i.e. whole bladder and/or BN/PU) and tumour progression as outcomes after a simultaneous endoscopic surgery of bladder tumour and BPH, as compared to TURBT alone. We queried PubMed and Web of Science database on 1 January 2020. We used random- and/or fixed-effects meta-analytic models in the presence or absence of heterogeneity according to the I 2 statistic, respectively., Results: Nine retrospective and three clinical trial studies were selected after considering inclusion and exclusion criteria. We conducted the meta-analysis on retrospective and randomised controlled trials (RCTs) separately. Eight retrospective and three RCT studies were included to assess the BN/PU recurrence risk and the summarised risk ratio (RR) was 1.02 (95% confidence interval [CI] 0.74-1.41) and 0.93 (95% CI 0.47-1.84), respectively. Five retrospective and two RCT studies were included to assess the progression risk and the summarised RR was 0.91 (95% CI 0.56-1.48) and 1.16 (95% CI 0.30-4.51), respectively. Eight retrospective and three RCT studies were included to assess the whole bladder recurrence risk and the summarised RR was 0.87 (95% CI 0.78-0.97) and 0.89 (95% CI 0.65-1.21), respectively., Conclusion: We did not observe any increased risk of total bladder recurrence, BN/PU recurrence, or progression after a simultaneous endoscopic surgery of bladder tumour and BPH, as compared to TURBT alone., (© 2020 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Purpose: Androgen deprivation therapy is a standard therapy for some patients with localized and almost all patients with metastatic prostate cancer. Although several clinical cohort studies have identified an impact of androgen deprivation therapy on cognitive function, the previous reviews were not able to perform a well designed quantitative synthesis to summarize the risk of dementia and/or Alzheimer disease. Consequently there is still a lack of systematic review and meta-analysis regarding the impact of this risk including more recent studies., Materials and Methods: We conducted a systematic review and meta-analysis of the literature assessing the differential incidence of dementia and/or Alzheimer disease as outcomes in patients with prostate cancer who did vs did not receive androgen deprivation therapy. We queried PubMed® and Web of Science™ databases from January 1 to 3, 2020. We used random or fixed effects meta-analytic models in the presence or absence of heterogeneity per the I 2 statistic. We performed 6 meta-analyses for all cause dementia, Alzheimer disease and all cause dementia or Alzheimer disease according to the duration of androgen deprivation therapy (up to 12 or more than 12 months)., Results: A total of 14 studies were selected after considering inclusion and exclusion criteria. Nine of them reported all cause dementia (ie all types of dementia including Alzheimer disease), with 8 reporting Alzheimer disease. Five studies assessed these outcomes according to the duration of androgen deprivation therapy. The risk of new onset dementia (all cause) and Alzheimer disease was higher in patients with prostate cancer who received androgen deprivation therapy compared to those who did not (HR 1.21, 95% CI 1.11-1.33 and HR 1.16, 95% CI 1.09-1.24). The risk of dementia (all cause) was higher in patients with prostate cancer who received androgen deprivation therapy for more than 12 months (HR 1.36, 95% CI 1.07-1.72); however, for those who had less than 12 months of androgen deprivation therapy exposure the difference was not statistically significant 1.06 (95% CI 0.77-1.28). There was no association between the androgen deprivation therapy duration and the risk of Alzheimer disease (HR 1.21, 95% CI 0.97-1.51 for exposure up to 12 months and HR 1.39, 95% CI 0.69-2.79 for exposure greater than 12 months)., Conclusions: Men who receive androgen deprivation therapy for prostate cancer have an increased risk of dementia and/or Alzheimer disease compared to men who do not receive androgen deprivation therapy; this was more pronounced when androgen deprivation therapy was given longer than 12 months.

Pharmacogenomics is a study of how the genome background is associated with drug resistance and how therapy strategy can be modified for a certain person to achieve benefit. The pharmacogenomics (PGx) testing becomes of great opportunity for physicians to make the proper decision regarding each non-trivial patient that does not respond to therapy. Although pharmacogenomics has become of growing interest to the healthcare market during the past five to ten years the exact mechanisms linking the genetic polymorphisms and observable responses to drug therapy are not always clear. Therefore, the success of PGx testing depends on the physician's ability to understand the obtained results in a standardized way for each particular patient. The review aims to lead the reader through the general conception of PGx and related issues of PGx testing efficiency, personal data security, and health safety at a current clinical level.

Introduction: The SuperPulse Thulium (Tm) fiber laser (wavelength of 1.94 m) has been recently introduced as a directed-energy source for urology. Preclinical studies have shown a significant potential of the SuperPulse Tm fiber laser (SP TFL) for lithotripsy. However, clinical reports of using SP TFL to treat urolithiasis are still few and limited. Of special interest are challenging cases, e.g., lower pole stones, when extreme deflection of the instrument is required., Objective: To evaluate the effectiveness of the SuperPulse Tm fiber laser in the management of lower pole small calyceal stones during flexible ureteroscopy (F-URS)., Method: s. The SuperPulse Tm fiber laser device (Urolase 2, IRE Polus, Fryazino, Russia) has been cleared for clinical use by the Ministry of Health of Russian Federation. Study protocol has been approved by the Ethical Review Committee. Between January 2018 and February 2019, 130 patients with kidney stones have undergone Thulium fiber laser lithotripsy during F-URS. We retrospectively analyzed 15 of this patients with a single radiopaque lower pole calculus that were included in the present study. Stone size, stone density, lithotripsy time (from the first to last footswitch press) and "lasering" (laser emission) time were measured. The SP TFL was used for stone disintegration with different settings in dusting and fragmentation modes (0.1 - 4J, 7-300Hz, 6-40W) via a fiber with a 200-m core diameter. Low dose CT scanning was performed on POD 90 to assess SFR., Results: Stone size ranged from 4 to 17 mm and stone density varied from 350 to 1459 HU. The average lithotripsy time was 12 min (3-30 min). The average "lasering" time was 1.3 min (0.4-2.5 min) and the mean hospital stay was 1.1+/-0.3 days. In all cases we reached the lower pole stone containing calyx with a laser fiber. The complication rates were evaluated by using the Clavien-Dindo grading system and did not exceed GII (6.6%). SFR on POD 90 was achieved in 86.6% of cases., Conclusions: F-URS with SuperPulse Tm fiber laser is safe and effective option in the management of lower pole small calyceal stones. The possibility of using small laser fibers gives better instrument deflection which make possible to reach lower pole calyceal stones even with acute lower pole infundibulopelvic angle (IPA).

Objective: Sarcosine was postulated in 2009 as a biomarker for prostate cancer (PCa). Here, we assess plasma sarcosine as a biomarker that is complementary to prostate-specific antigen (PSA)., Methods: Plasma sarcosine was measured using gas chromatography-mass spectrometry (GC-MS) in adults classified as noncancerous controls (with benign prostate hyperplasia [BPH], n = 36), with prostatic intraepithelial neoplasia (PIN, n = 16), or with PCa (n = 27). Diagnostic accuracy was assessed using receiver operating characteristic curve analysis., Results: Plasma sarcosine levels were higher in the PCa (2.0 µM [1.3-3.3 µM], P <.01) and the PIN (1.9 µM [1.2-6.5 µM], P <.001) groups than in the BPH (0.9 µM [0.6-1.4 µM]) group. Plasma sarcosine had "good" and "very good" discriminative capability to detect PIN (area under the curve [AUC], 0.734) and PCa (AUC, 0.833) versus BPH, respectively. The use of PSA and sarcosine together improved the overall diagnostic accuracy to detect PIN and PCa versus BPH., Conclusion: Plasma sarcosine measured by GC-MS had "good" and "very good" classification performance for distinguishing PIN and PCa, respectively, relative to noncancerous patients diagnosed with BPH., (© American Society for Clinical Pathology 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The individual clinical significance of a positive surgical margin (PSM) after radical prostatectomy has remained controversial. Studies have suggested that the Gleason grade (GG) at the PSM could improve predictive accuracy and decision making. Our objective was to systematically review the reported data to determine the effect of the GG at the PSM on the prognosis after radical prostatectomy. A systematic review was conducted by searching MEDLINE/PubMed for studies reported by June 2019 in accordance with the Preferred Reporting Items for Systematic Review statement. The keywords used included prostate cancer, radical prostatectomy, positive surgical margin, Gleason score, and/or Gleason grade. After a systematic literature review, 10 studies were included, comprising 14,108 patients, of whom 2454 (17.4%) had a PSM and 428 (14%) eventually experienced biochemical recurrence (BCR) within a median follow-up of 18 to 156 months. Data on neoadjuvant or adjuvant therapy were not estimable. In a meta-analysis, GG4 at PSM was significantly associated with BCR compared with GG3 (pooled hazard ratio, 1.87; 95% confidence interval, 1.53-2.28; z = 6.16). The Cochrane Q test (χ 2  = 5.88; P = .318) and I 2 test (I 2  = 15.0%) showed that no significant heterogeneity was present. GG4 at a PSM is a feature of biologically and clinically aggressive prostate cancer that is associated with a significant increase risk of BCR. GG at PSM should be recorded in each pathological report. Given this adverse prognostic value patients with GG4 at the PSM should be considered for multimodal therapy such as radiotherapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The purpose of this study was to assess the prognostic value of hemoglobin (Hb) in patients with metastatic hormone-sensitive prostate cancer (HSPC). The PUBMED, Web of Science, Cochrane Library, and Scopus databases were searched in December 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared patients with HSPC with normal and low Hb levels to determine their ability to predict overall survival, cancer-specific survival, progression-free survival, and castration-resistant prostate cancer-free survival. Formal meta-analyses were performed for these outcomes. The systematic review identified 25 studies including 6614 patients; 21 studies comprising 5782 patients were eligible for meta-analysis. Low Hb levels were associated with worse overall survival (pooled hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.15-1.29), cancer-specific survival (pooled HR, 1.46; 95% CI, 1.24-1.72), progression-free survival (pooled HR, 1.21; 95% CI, 1.14-1.28), and castration-resistant prostate cancer-free survival (pooled HR, 1.37; 95% CI: 1.18-1.57). Subgroup analyses revealed that low Hb levels were also associated with poor overall survival in patients with both "high-volume" (pooled HR, 1.49; 95% CI, 1.29-1.72) and "low-volume" HSPC (pooled HR, 1.40; 95% CI, 1.13-1.73). This meta-analysis revealed that low Hb serum levels in patients with metastatic HSPC were associated with increased risks of overall mortality, cancer-specific mortality, disease progression, and biochemical recurrence. Furthermore, Hb levels were independently associated with overall survival in the "high-volume" and "low-volume" HSPC subgroups. Therefore, it might be useful to incorporate Hb testing into prognostic tools for metastatic HSPC., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To assess the outcomes of surgical repair of anterior apical prolapse using the 6-strap mesh implant., Study Design: The prospective study included 100 patients with genitourinary prolapse. We used advanced 6-strap mesh implant. The results were assessed at 1 (n = 100) and 12 (n = 93) months after surgery. Maximum follow-up was over 4 years. The anatomical outcomes according to the Pelvic Organ Prolapse Quantification system and intraoperative and postoperative complications were assessed. Stage II and higher prolapse was considered to be a recurrence. The quality of life and sexual function were assessed using Pelvic Organ Prolapse Distress Inventory 20, Pelvic Floor Impact Questionnaire 7, and Pelvic Organ Prolapse/Incontinence Sexual Questionnaire 12., Results: Median age was 57 years (34-78 years (95% confidence interval)). All patients had stage III cystocele. The anterior vaginal wall descent in all the patients was associated with uterine descent: 37 (37%), stage II; 60 (60%), stage III; in 3 (3%), stage IV. In eight cases, postoperative de novo stress urinary incontinence developed. The quality of life improved in 93 (93%) women as judged by the Pelvic Floor Distress Inventory 20 data and in 87 (87%) women, according to the Pelvic Floor Impact Questionnaire 7 data. The desirable anatomical result (⩽stage I according to the Pelvic Organ Prolapse Quantification system) was achieved in 97 (97%) patients. With the exception of mesh fragment excision due to erosion (grade 3a), all the complications were classified as grade I according to the Clavien-Dindo classification., Conclusion: Genitourinary prolapse repair using 6-strap mesh is efficacious and relatively safe. The method demonstrates good anatomical results in relation to both anterior and apical prolapses with relatively short-term complications.

Purpose: We assessed the prognostic value of sex differences in upper tract urothelial carcinoma and urothelial carcinoma of the bladder treated with radical surgery., Materials and Methods: The PubMed®, Web of Science®, Cochrane Library and Scopus® databases were searched in July 2019 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Studies were deemed eligible if they compared overall, cancer specific, and recurrence-free survival in patients with upper tract urothelial carcinoma and urothelial carcinoma of the bladder. Formal meta-analyses were performed for these outcomes according to sex differences., Results: Overall 66 studies with 100,389 patients with urothelial carcinoma of the bladder and 40 studies with 39,759 patients with upper tract urothelial carcinoma were eligible for review and meta-analysis. Female patients with urothelial carcinoma of the bladder were associated with worse cancer specific survival (pooled HR 1.20, 95% CI 1.10-1.31), overall survival (pooled HR 1.03, 95% CI 1.01-1.05) and recurrence-free survival (pooled HR 1.13, 95% CI 1.02-1.25). In contrast, those with upper tract urothelial carcinoma were not associated with cancer specific survival (pooled HR 0.94, 95% CI 0.89-1.00), overall survival (pooled HR 0.98, 95% CI 0.95-1.01) and recurrence-free survival (pooled HR 0.90, 95% CI 0.78-1.03)., Conclusions: Sex is associated with cancer specific mortality, overall mortality and disease recurrence in urothelial carcinoma of the bladder but not in upper tract urothelial carcinoma. Given the genetic and social differences between the sexes, sex differences may represent a key factor in the clinical decision making process.

Introduction: The metabolic alterations reflecting the influence of prostate cancer cells can be captured through metabolomic profiling., Objective: To characterize the plasma metabolomic profile in prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa)., Methods: Metabolomics analyses were performed in plasma samples from individuals classified as non-cancerous control (n = 36), with PIN (n = 16), or PCa (n = 27). Untargeted [26 moieties identified after pre-processing by gas chromatography/mass spectrometry (GC/MS)] and targeted [46 amino acids, carbohydrates, organic acids and fatty acids by GC/MS, and 16 nucleosides and amino acids by ultra performance liquid chromatography-triple quadrupole/mass spectrometry (UPLC-TQ/MS)] analyses were performed. Prostate specific antigen (PSA) concentrations were measured in all samples. In PCa patients, the Gleason scores were determined., Results: The metabolites that were best discriminated (p < 0.05, FDR < 0.2) for the Kruskal-Wallis test with Dunn's post-hoc comparing the control versus the PIN and PCa groups included isoleucine, serine, threonine, cysteine, sarcosine, glyceric acid, among several others. PIN was mainly characterized by alterations on steroidogenesis, glycine and serine metabolism, methionine metabolism and arachidonic acid metabolism, among others. In the case of PCa, the most predominant metabolic alterations were ubiquinone biosynthesis, catecholamine biosynthesis, thyroid hormone synthesis, porphyrin and purine metabolism. In addition, we identified metabolites that were correlated to the PSA [i.e. hypoxanthine (r = - 0.60, p < 0.05; r = - 0.54, p < 0.01) and uridine (r = - 0.58, p < 0.05; r = - 0.50, p < 0.01) in PIN and PCa groups, respectively] and metabolites that were significantly different in PCa patients with Gleason score < 7 and ≥ 7 [i.e. arachidonic acid, median (P25-P75) = 883.0 (619.8-956.4) versus 570.8 (505.6-651.8), respectively (p < 0.01)]., Conclusions: This human plasma metabolomic assessment contributes to the understanding of the unique metabolic features exhibited in PIN and PCa and provides a list of metabolites that can have the potential to be used as biomarkers for early detection of disease progression and management.

Introduction and Objectives: To evaluate the prognostic role of modified Glasgow prognostic score (mGPS) for the prediction of oncological outcomes in a retrospective large multicenter cohort of upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU)., Materials and Methods: We retrospectively analyzed a multicenter cohort of patients treated with RNU for clinically nonmetastatic UTUC. Multivariable logistic regression analyses were performed to evaluate the ability of mGPS to predict nonorgan confined (NOC) disease and lymph-node involvement (LNI) at RNU. Multivariable Cox-regression models were performed to evaluate the preoperative and postoperative prognostic effect of mGPS on survival outcomes., Results: Overall, 2,492 patients were included in the study. Of these, 1,929 (77%), 530 (21%), and 33 (1%) had a mGPS of 0, 1, and 2, respectively. mGPS was associated with characteristics of tumor aggressiveness and independently predicted LNI and NOC at RNU (both P < 0.05). On univariable and multivariable Cox-regression analyses, higher mGPS was independently associated with recurrence-free, cancer-specific, and overall survival, both in a preoperative and in a postoperative setting. The inclusion of mGPS significantly improved the discrimination of a preoperative model for the prediction of oncologic outcomes compared to standard prognosticators., Conclusions: We found that mGPS is independently associated with clinicopathologic features and survival outcomes after RNU. Future studies should investigate the role of mGPS in a panel of preoperative markers for the prediction of NOC and LNI in UTUC patients, thus possibly improving the selection for perioperative systemic therapy., Competing Interests: Conflicts of interest I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript are the following: Shahrokh Shariat owns or co-owns the following patents: Methods to determine prognosis after therapy for prostate cancer. Granted 2002-09-06. Methods to determine prognosis after therapy for bladder cancer. Granted 2003-06-19. Prognostic methods for patients with prostatic disease. Granted 2004-08-05. Soluble Fas: urinary marker for the detection of bladder transitional cell carcinoma. Granted 2010-07-20. He is advisory board member of Astellas, Cepheid, Ipsen, Jansen, Lilly, Olympus, Pfizer, Pierre Fabre, Sanofi, and Wolff. He is speaker for Astellas, Ipsen, Jansen, Lilly, Olympus, Pfizer, Pierre Fabre, Sanochemia, Sanofi, and Wolff. The other authors made no disclosures., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To validate the predictive and prognostic role of the De Ritis ratio in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy in a large multi-institutional cohort., Materials and Methods: The preoperative De Ritis ratio was assessed in a multi-institutional cohort of 2,492 patients. An altered De Ritis ratio was defined as a ratio >1.35. Logistic regression analyses were performed to assess the association of the De Ritis ratio with advanced disease. The association of the De Ritis ratio with survival outcomes was evaluated using Cox proportional hazards regression models., Results: An altered De Ritis ratio was observed in 985 (41.5%) patients; it was associated with a more advanced pathological features. In a preoperative model, the De Ritis ratio was an independent predictive factor for the presence of lymph node metastasis and muscle-invasive and nonorgan-confined disease (P < 0.05). Compared to patients with a normal De Ritis ratio, those with an altered De Ritis ratio had worse recurrence free (P <0.0001), cancer specific (P = 0.0003), and overall survival (P = 0.0014) in the Kaplan-Meier analyses. In the multivariable analyses that was adjusted for the effects of standard clinicopathologic features, the De Ritis ratio did not retain its independent prognostic value., Conclusions: In UTUC, the preoperative De Ritis ratio is associated with adverse clinicopathologic features and independently predicts features of biologically and clinically aggressive UTUC. Therefore, it might be useful to incorporate the De Ritis ratio into prognostic tools in selecting appropriate treatment strategies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: We sought to assess the prognostic value of variant histology in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy., Materials and Methods: We searched PubMed®, Web of Science™, Cochrane Library and Scopus® databases in May 2019 according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Studies were deemed eligible if they compared overall, cancer specific and recurrence-free survival in patients with upper tract urothelial carcinoma with or without variant histology. Formal meta-analyses were performed for these outcomes., Results: We identified 32 studies with 16,052 patients, including 26 studies with 12,865 patients that were eligible for the meta-analysis. Variant histology was associated with poor outcomes in terms of cancer specific (pooled HR 2.00, 95% CI 1.57 to 2.56), overall (pooled HR 1.76, 95% CI 1.51 to 2.04) and recurrence-free survival (pooled HR 1.64, 95% CI 1.42 to 1.89). Subgroup analyses revealed that micropapillary (pooled HR 3.02, 95% CI 1.71 to 5.34), and squamous and/or glandular variant histologies (pooled HR 1.48, 95% CI 1.14 to 1.92) were also associated with poor cancer specific survival., Conclusions: Variant histology in patients with upper tract urothelial carcinoma is associated with an increased risk of cancer specific and overall mortality and disease recurrence. Furthermore, variant histology was independently associated with cancer specific survival in the micropapillary, and squamous and/or glandular variant histology subgroups. It may be useful to incorporate variant histology into prognostic tools that help guide patients and physicians in selecting appropriate treatment strategies for upper tract urothelial carcinoma.

Purpose: To assess the prevalence of sarcopenia and whether body composition parameters are associated with disease progression and overall survival (OS) in castration-resistant prostate cancer (CRPC) patients., Materials and Methods: This single-centre retrospective study evaluated data of 186 consecutive patients who underwent chemohormonal therapy between 2005 and 2016 as first-line systemic treatment for CRPC. Skeletal muscle and fat indices were determined using computerized tomography data before initiation of chemotherapy. Sarcopenia was defined as SMI of <55 cm 2 /m 2 . Visceral-to-subcutaneous fat ratio and skeletal muscle volume were calculated with body composition specific areas. Harrell's concordance index was used for predictive accuracy., Results: A total of 154 (82.8%) patients met the criteria for sarcopenia; 139 (74.7%) individuals completed at least six cycles of docetaxel. Within a median follow-up of 24.1 months, age (HR 1.03, 95% CI 1.01-1.06, p = 0.02), high PSA (1.55, 95% CI 1.07-2.25, p = 0.02) and low skeletal muscle volume (HR 1.61, 95% CI 1.10-2.35, p = 0.02) were the only independent prognostic factor for tumor progression. Overall, 93 (50%) patients died during the follow-up period. The established prognosticator, the prechemotherapy presence of liver metastases (HR 1.32, 95% CI 1.08-1.61, p < 0.01) was associated with shorter OS. Moreover, we noted that patients with an elevated visceral-to-subcutaneous fat ratio tended to have a shorter OS (p = 0.06)., Conclusion: The large majority of men with CRPC suffers from sarcopenia. In our cohort, low skeletal muscle volume was an independent adverse prognosticator for progression of disease. We could not detect a statistically significant body composition parameter for OS, although patients with a high proportion of visceral fat had a trend for shorter OS. However, we suggest that body composition parameters determined by CT data can provide useful objective prognostic factors that may support tailored treatment decision-making.

Background: To identify predictors of survival in patients treated with docetaxel chemotherapy for castration-resistant prostate cancer (CRPC)., Methods: We retrospectively analyzed clinical data from 186 patients who underwent docetaxel chemotherapy for CRPC from 2005 to 2016 at a single center. Pretreatment baseline variables including demographic and clinicopathological data were reviewed. Disease progression was defined by imaging and/or consecutive prostate-specific antigen (PSA) elevation. The systemic immune-inflammation index (SII), the modified Glasgow Prognostic Score (mGPS), and the neutrophil-lymphocyte ratio (NLR) were calculated. Univariable and multivariable Cox proportional hazards regression analyses reporting hazard ratios assessed the risk for disease progression and overall survival (OS). A survival nomogram was constructed., Results: Most patients (n = 139, 74.7%) completed at least 6 cycles of docetaxel chemotherapy. 156 patients (82.9%) experienced disease progression during the studied period. Only mGPS was independently associated with disease progression in a multivariable model (P < 0.01). During the studied period, 98 patients (52.1%) died. The built survival nomogram included statistically significant variables for OS in univariable analysis: hemoglobin, PSA, alkaline phosphatase (AP), lactate dehydrogenase, SII, neutrophil-lymphocyte ratio, mGPS, and site of metastases; and had a concordance index of 0.703. At decision curve analysis, the nomogram led to superior outcomes for any decision associated with a threshold probability of above 40%. In multivariable analysis, only AP (P = 0.02), hemoglobin and PSA (P < 0.01, respectively) remained associated with OS., Conclusions: PSA, AP, and hemoglobin are independent prognosticators for OS. Although mGPS is a promising marker for tumor progression and SII is a plausible prognostic marker for OS, valid integration of inflammatory indices into a prognostic model requires validation studies. Predictive and prognostic biomarkers are desperately needed to guide physicians in treatment counseling given the heterogeneous nature of CRPC and the plethora of effective therapies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To evaluate the clinical prognostic value of preoperative serum De Ritis ratio (DRR; aspartate aminotransferase/alanine aminotransferase) on postoperative survival outcomes in patients with radiation-recurrent prostate cancer (PCa) who underwent salvage radical prostatectomy (SRP)., Patients and Methods: A retrospective review was conducted of patients with radiation-recurrent PCa who underwent SRP in five tertiary referral centres from 2007 to 2015. An increased preoperative serum DRR was defined as ≥1.35. The association between DRR and postoperative outcomes was tested. Multivariate Cox analyses were performed to identify the independent predictors of biochemical recurrence (BCR), metastases-free survival (MFS), overall survival (OS), and cancer-specific survival (CSS)., Results: Overall 214 patients underwent SRP, of them 98 (45.8%) with a high serum DRR were included in the study. In a multivariate analysis high DRR was an independent predictor of BCR [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.16-2.78; P = 0.009]. No significant association was found between preoperative DRR and MFS (HR 1.32, 95% CI 0.53-3.30; P = 0.55), OS (HR 2.35, 95% CI 0.84-6.57; P = 0.10), and CSS (HR 3.36, 95% CI 0.65-17.35; P = 0.15)., Conclusion: Increased preoperative serum DRR is associated with the development of BCR in patients with radiation-recurrent PCa who underwent SRP. DRR might serve as an early indicator of BCR, which may facilitate recognition of potential relapse and could translate into more intense follow-up and even salvage therapy in selected patients., Abbreviations: ADT: androgen-deprivation therapy; BCR, biochemical recurrence; BCRFS: BCR-free survival; CSS: cancer-specific survival; DRR: De Ritis ratio; HR: hazard ratio; MFS: metastasis-free survival; PCa: Prostate Cancer; OS: overall survival; PLND: pelvic lymph node dissection; (EB)RT: (external beam) radiotherapy; SRP: salvage radical prostatectomy., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Purpose: To assess the prognostic significance of the nuclear receptor binding SET protein 2 (NSD2), a co-activator of the NFkB-pathway, on tumour progression in patients with advanced prostate cancer (PCa). Methods: We retrospectively assessed NSD2 expression in 53 patients with metastatic and castration-resistant PCa. Immunohistochemical staining for NSD2 was carried out on specimen obtained from palliative resection of the prostate. Univariable and multivariable analyses were performed to assess the association between NSD2 expression and PCa progression. Results: Of the 53 patients, 41 had castration-resistant PCa and 48 men had metastases at time of tissue acquisition. NSD2 expression was increased in tumour specimen from 42 patients (79.2%). In univariable Cox regression analyses, NSD2 expression was associated with PSA progression, progression on imaging and overall survival ( p  = 0.04, respectively). In multivariable analyses, NSD2 expression did not retain its association with these endpoints. Conclusions: NSD2 expression is abnormal in almost 80% of patients with advanced PCa. Expression levels of this epigenetic regulator are easily detected by immunohistochemistry while this biomarker exhibited prognostic value for PCa progression and death in univariable analysis. Further studies on NSD2 involvement in PCa proliferation, progression, metastasis and resistance mechanisms are needed.

Background: The purpose of this study was to compare the efficacy of 2 bacillus Calmette-Guérin (BCG) strains, BCG-Tice and BCG-Moreau, in the treatment of non-muscle-invasive bladder cancer (NMIBC)., Materials and Methods: We retrospectively reviewed clinical data from patients treated with BCG for NMIBC at 3 academic centers. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox proportional hazards regression analyses were used to compare recurrence-free (RFS) and progression-free survival (PFS) of patients in the 2 treatment groups. In addition, we performed exploratory analyses of treatment effect according to the receipt of adequate BCG treatment, high-risk disease, age, gender, smoking status, pathologic stage, and pathologic grade., Results: A total of 321 (48.6%) patients were treated with BCG-Tice and 339 (51.4%) with BCG-Moreau. IPTW-adjusted Cox proportional hazard regression analysis did not show a difference in RFS (hazard ratio, 0.88; 95% confidence interval, 0.56-1.38; P = .58) or PFS (hazard ratio, 0.55; 95% confidence interval, 0.25-1.21, P = .14) between BCG-Tice and BCG-Moreau. On subgroup analyses, we could not identify an association of BCG strain with outcomes., Conclusions: There was no difference in RFS and PFS between BCG-Tice and BCG-Moreau strains in the adjuvant treatment of NMIBC. However, we confirmed the importance of maintenance therapy for achieving a sustainable response in patients with intermediate- and high-risk NMIBC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To assess the prognostic value of alkaline phosphatase in patients with hormone-sensitive prostate cancer., Methods: A systematic review and meta-analysis was performed using the PUBMED, Web of Science, Cochrane Library, and Scopus in April 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared hormone-sensitive prostate cancer patients with high vs. low alkaline phosphatase to determine its predictive value for overall survival, cancer-specific survival, and progression-free survival. We performed a formal meta-analysis of these outcomes., Results: 42 articles with 7938 patients were included in the systematic review and 28 studies with 5849 patients for the qualitative assessment. High alkaline phosphatase was associated with worse overall survival (pooled HR 1.72; 95% CI 1.37-2.14) and progression-free survival (pooled HR 1.30; 95% CI 1.10-1.54). In subgroup analyses of patients with "high-volume" and "low-volume", alkaline phosphatase was associated with the overall survival (pooled HR 1.41; 95% CI 1.21-1.64 and pooled HR 1.64; 95% CI, 1.06-2.52, respectively)., Conclusions: In this meta-analysis, elevated serum levels of alkaline phosphatase were associated with an increased risk of overall mortality and disease progression in patients with hormone-sensitive prostate cancer. In contrast, those were not associated with an increased risk of cancer-specific mortality. Alkaline phosphatase was independently associated with overall survival in both patients with "high-volume" and "low-volume" hormone-sensitive prostate cancer. Alkaline phosphatase may be useful for being integrated into prognostic tools that help guide treatment strategy, thereby facilitating the shared decision making process.

Background: Colorectal cancer (CRC) at a current clinical level is still hardly diagnosed, especially with regard to nascent tumors, which are typically asymptotic. Searching for reliable biomarkers of early diagnosis is an extremely essential task. Identification of specific post-translational modifications (PTM) may also significantly improve net benefits and tailor the process of CRC recognition. We examined depleted plasma samples obtained from 41 healthy volunteers and 28 patients with CRC at different stages to conduct comparative proteome-scaled analysis. The main goal of the study was to establish a constellation of protein markers in combination with their PTMs and semi-quantitative ratios that may support and realize the distinction of CRC until the disease has a poor clinical manifestation. Results: Proteomic analysis revealed 119 and 166 proteins for patients in stages I-II and III-IV, correspondingly. Plenty of proteins (44 proteins) reflected conditions of the immune response, lipid metabolism, and response to stress, but only a small portion of them were significant ( p < 0.01) for distinguishing stages I-II of CRC. Among them, some cytokines (Clusterin (CLU), C4b-binding protein (C4BP), and CD59 glycoprotein (CD59), etc.) were the most prominent and the lectin pathway was specifically enhanced in patients with CRC. Significant alterations in Inter-alpha-trypsin inhibitor heavy chains (ITIH1, ITIH2, ITIH3, and ITIH4) levels were also observed due to their implication in tumor growth and the malignancy process. Other markers (Alpha-1-acid glycoprotein 2 (ORM2), Alpha-1B-glycoprotein (A1BG), Haptoglobin (HP), and Leucine-rich alpha-2-glycoprotein (LRG1), etc.) were found to create an ambiguous core involved in cancer development but also to exactly promote tumor progression in the early stages. Additionally, we identified post-translational modifications, which according to the literature are associated with the development of colorectal cancer, including kininogen 1 protein (T327-p), alpha-2-HS-glycoprotein (S138-p) and newly identified PTMs, i.e., vitamin D-binding protein (K75-ac and K370-ac) and plasma protease C1 inhibitor (Y294-p), which may also contribute and negatively impact on CRC progression. Conclusions: The contribution of cytokines and proteins of the extracellular matrix is the most significant factor in CRC development in the early stages. This can be concluded since tumor growth is tightly associated with chronic aseptic inflammation and concatenated malignancy related to loss of extracellular matrix stability. Due attention should be paid to Apolipoprotein E (APOE), Apolipoprotein C1 (APOC1), and Apolipoprotein B-100 (APOB) because of their impact on the malfunction of DNA repair and their capability to regulate mTOR and PI3K pathways. The contribution of the observed PTMs is still equivocal, but a significant decrease in the likelihood between modified and native proteins was not detected confidently.

Purpose of Review: Conventional transurethral resection of bladder tumor (cTURBT) is the standard approach to the diagnosis and treatment of nonmuscle invasive bladder cancer. However, it suffers from inherent limitations such as insufficient assessment of resection depth and the need for intravesical tumor fragmentation that hampers histopathological evaluation. We summarize recent clinical data on en bloc resection of bladder tumor (ERBT), a method that promises to overcome these limitations., Recent Findings: The PubMed/Medline databases were searched for reports on ERBT focusing on trends in the last 2 years. ERBT provides greater resection quality, making up to 95% of detrusor muscle available for pathological evaluation. ERBT also allows detection of the muscularis mucosae thus facilitating T1 substaging. Available data demonstrate no significant difference in perioperative morbidity. No conclusions can be drawn on the impact of either modality on tumor recurrence and progression, as the available data is too underpowered., Summary: ERBT is gaining acceptances as there is increasing evidence that it improves the quality of resected specimens. There seems to be no difference in perioperative morbidity between ERBT and cTURBT. The impact of ERBT on important endpoints such as recurrence and progression remains to be fully elucidated in further studies.

Currently, prostate cancer (PCa) is one of the most important problem of modern medicine, including economical issue. The detection of PCa compared to any other cancers progressively increases with age. Currently, PCa is the most commonly diagnosed solid tumor. Radical prostatectomy and radiation therapy are considered standard of treatment for PCa. However, while excellent long-term oncologic results can be achieved, these methods are often associated with significant complication rate, which negatively affects the quality of life of patients. Technological advancement and their implementation in medicine have increased treatment opportunities in oncourology. The purpose of this literature review is to study alternative treatment methods of localized PCa and compare their efficiency with conventional therapy.

The purpose of this study was to assess the prognostic value of lactate dehydrogenase (LDH) in patients with metastatic prostate cancer (PC). A systematic review and meta-analysis was performed in March 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared patients with PC with high versus low LDH to determine the predictive value of LDH for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). We performed a formal meta-analysis for both OS and PFS. A total of 59 articles with 14,851 patients were included in the systematic review and 45 studies with 12,224 patients for the qualitative assessment. High LDH was associated with both worse OS (pooled hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.75-2.44) and PFS (pooled HR, 1.08; 95% CI, 1.01-1.16). In subgroup analyses of both patients with castration-resistant prostate cancer (CRPC) and those with hormone-sensitive prostate cancer (HSPC), LDH was associated with OS (pooled HR, 2.02; 95% CI, 1.69-2.42 and pooled HR, 2.25; 95% CI, 1.78-2.84, respectively). In patients with CRPC, LDH was associated with OS in those treated with docetaxel systemic chemotherapy and androgen receptor-axis-targeting agents (pooled HR, 2.03; 95% CI, 1.37-3.00 and pooled HR, 1.79; 95% CI, 1.25-2.57, respectively). Elevated serum levels of LDH were associated with an increased risk of mortality and progression in patients with metastatic PC. LDH was independently associated with OS in both patients with CRPC and HSPC. LDH could be integrated into prognostic tools that help guide treatment strategy, thereby facilitating the shared decision-making process., (Copyright © 2019. Published by Elsevier Inc.)

Laser technology has taken a place among the methods of treatment of various urological diseases. The new laser devices are being developed in addition to commonly used. Physicists of the russian NTO "IRE Polus" in collaboration with doctors from Sechenov University have developed a new generation laser device - thulium fiber laser. It has been actively used since 2017 for laser enucleation of prostate. Later the laser was used for treatment of bladder tumor, lithotripsy. The device has already managed to prove its efficacy in in-vitro experiments and clinical practice surpassing foreign analogues.

In the Russian Federation, a proportion of bladder cancer in the overall structure of malignant tumors is about 2.8% and among oncological diseases of genitourinary system its incidence is second only to prostate cancer. Bladder cancer ranks as ninth most prevalent in males and as eighteens in females. The most important issue is to determine a recurrence rate of non-muscle invasive bladder cancer, which can reach 80%. In this regard, currently, all over the world much more attention is paid to studying and creation of early detection, including non-invasive, which will be reliable in the early stages. It can possibly lead to a reduction the number of cystoscopy and become as "golden" standard of non-invasive diagnosis bladder cancer.

Aim: Experimental evaluation of the efficacy and safety of lithotripsy using a new pulsed thulium fiber laser operating at a wavelength of 1.94 microns, peak power of 500 watts (maximum average power of 50 watts) by comparing it with a holmium laser operating at a wavelength of 2.1 microns (average maximum power 100 W and 120 W)., Relevance: The proportion of minimally invasive surgery in the management of urolithiasis, including retrograde intrarenal surgery, is steadily growing. The most appropriate tool for stone destruction is a laser. To date, the gold standard of minimally invasive surgical treatment of nephrolithiasis is holmium laser lithotripsy, which uses a laser on yttrium-aluminum-garnet activated by holmium ions (Ho: YAG) operating at a wavelength of 2.1 m. However, in recent years, lasers on a Tm-activated fiber with a wavelength of 1.94 m have become increasingly popular since the water absorption coefficient for the Tm radiation of a fiber laser is 5.5 times higher than for a Ho: YAG laser and in 2.2 times higher than for the Tm: YAG laser. This difference may translate into greater effectiveness and speed of stone crushing, which in turn leads to shorter operating time., Materials and Methods: This article describes physical foundations of holmium and thulium laser radiation, the mechanisms of stone fragmentation, data from a series of experiments comparing the efficiency and safety of ex-vivo lithotripsy using a holmium solid-state laser with a wavelength of 2.1 m and a thulium fiber laser with a wavelength of 1.94 m., Results: The study findings suggest that the STA IRE-Polyus thulium fiber laser operating at a wavelength of 1.94 microns and a maximum power of 500 watts has several advantages over the holmium laser in the stone fragmentation in urological practice., Conclusion: The results of the experimental work allow us to conclude that the use of a thulium fiber laser operating at a wavelength of 1.94 m and a maximum peak power of 500 W enables highly effective and safe lithotripsy.

Relevance: Acute uncomplicated lower urinary tract infections (AULUTI) are one of the most common diseases in urological practice. The management of cystitis is commonly based on antibacterial therapy. Despite the high efficiency, inadequate prescription of antibiotics leads to an increase in microorganisms resistance. In light of these matters, the selection of antibacterial agents to which the sensitivity of bacteria is the highest is becoming increasingly challenging., Aim: To estimate the spectrum and local sensitivity of E. coli in patients with AULUTI., Materials and Methods: The present study analyzed the results of bacterial culture sampled from 45 patients with AULUTI. The mean age of the patients was 44+/-17 years. All bacterial cultures were obtained in out-patient settings in the framework of a multicenter initiative study on the prevention of recurrent AULUTI with d-mannose., Results: Microbiological studies of the urine of patients with AULUTI revealed the growth of E. coli in concentrations ranging from 104 to 107 CFU/ml. Assessment of sensitivity demonstrated 100% sensitivity of Escherichia coli to fosfomycin trometamol., Conclusion: According to the findings of microbiological studies, the patients with the AULUTI retain the highest sensitivity level of E.coli to phosphomycin trometamol, which allows it to be used as a first-line drug.

Introduction: Prostate cancer is one of the most common types of cancer in men. The gold standard for the detection of prostate cancer is ultrasound guided transrectal prostate biopsy. The detectability of cancer using this method is from 30 to 50%. As a result, many men undergo multiple repeat biopsies for suspected prostate cancer. The European Association of Urology does not give any recommendations on this matter. A revolutionary new method in the diagnosis of prostate cancer is a targeted prostate biopsy using a fusion of multiparametric magnetic resonance imaging (MRI) and ultrasound., Materials and Methods: At the R.M. Fronstein Clinic of Urology, 55 patients with suspected prostate cancer from September 2017 to January 2018 underwent fusion prostate biopsy. Of them, 21 patients had negative primary biopsies. Two patients had verified prostate cancer. 32 patients did not undergo primary biopsies., Results: The findings of the study suggest that using MRI-ultrasound fusion for guidance of targeted prostate biopsy improves the quality of the histological material, allows patients to avoid unnecessary biopsy, reduces the number of punctures, thereby offering higher diagnostic performance in detecting prostate cancer. MRI-ultrasound fusion targeted biopsy has a high sensitivity in detecting clinically significant cancer and low for clinically insignificant cancers., Conclusion: The technique affords accurate detection of the location and extent of pathological lesions in the prostate thus allowing focal therapy for prostate cancer.

Introduction: Some authors consider HoLEP a new gold standard for the surgical management of prostatic hyperplasia. The increasing utilization of holmium enucleation has led to the development of various modifications of this treatment modality, including the so-called enucleation as a single piece (HoLEP en bloc), which reduces the operative time and, according to some authors, facilitates acquiring new surgical technique by surgical trainees., Aim: To compare the effectiveness and safety of the traditional HoLEP and HoLEP en bloc., Materials and Methods: The study comprised 227 BPH patients aged from 53 to 86 years old (mean - 61.38+/-5.09 years). HoLEP en bloc was performed in 114 patients, of whom 39 patients had prostate volume (Vpr) less than 80 cm3, and in 75 patients it was more than 80 cm3. The standard HoLEP was performed in 113 patients, of whom 41 patients had Vpr less than 80 cm3, and in 72 patients it was more than 80 cm3., Results: Enucleation time: HoLEP - 48+/-12 min, HoLEP en-bloc - 35+/-10; morcellation time: HoLEP - 20+/-3 min, HoLEP en-bloc - 16+/-12; duration of urinary bladder drainage by a urethral catheter: HoLEP - 58+/-3 h, HoLEP en-bloc - 41+/-2; length of hospital stay: HoLEP - 5.93+/-0.39 days, HoLEP en-bloc - 4.45+/-0.35; bladder tamponade, urethrocystoscopy and coagulation of bleeding vessels: HoLEP-3, HoLEP en-bloc-1; infectious-inflammatory complications (prostatitis): HoLEP-3, HoLEP en-bloc-2; acute urinary retention, stress urinary incontinence: HoLEP-6, HoLEP en-bloc-2; stress urinary incontinence: HoLEP - 5, HoLEP en-bloc - 2., Conclusion: En bloc holmium enucleation of the prostate results in the reduction of enucleation and total operative time compared with traditional HoLEP due to the fast identification of the surgical capsule and the right layer. Using this technique can improve the effectiveness of learning holmium laser enucleation of the prostate by surgical trainees.

Aim: To evaluate early prostate cancer cryoablation functional and oncological results in comparison with results of extraperitoneoscopic radical prostatectomy., Materials and Methods: We analyzed early results of surgical treatment of 285 patients with prostate cancer: 42 of them had undergone total cryoablation (Group 1) while the rest of them had been treated by radical laparo- and extraperitoneoscopic prostatectomy. For comparative assessment of prostate cryoablation results, 42 patients from Group 2 randomized in accordance with their age, stage of disease, Gleason, prostate-specific antigen, and prostate volume were selected. In compliance with the results of pre-surgical examination, all the patients had low oncological risk and were not concerned in sexual function. Volume of prostate was from 22 to 65 cm 3 , prostate-specific antigen level was from 4.1 to 10 ng/mL, and level of neoplastic process differentiation using Gleason grading system was from 6 to 7a (3 + 4) scores., Results: Patients after prostate cryoablation in early post-surgical period felt lower intensity of postoperative pain compared with those who had undergone prostatectomy. Follow-up period up to 12 months manifested significant true reduction of prostate-specific antigen level in both groups of patients. Frequency of stress-induced enuresis in Group 1 was not observed., Conclusion: Radical prostatectomy is still the traditional treatment of choice in the case of localized prostate cancer. But we can draw the conclusion that cryoablation is an effective low-invasive method for treatment of low oncological risk patients, which gives the opportunity both to achieve good oncological results and to preserve high life quality.

Endoscopic enucleation of the prostate (EEP) techniques such as HoLEP (holmium laser enucleation of the prostate), ThuLEP (thulium laser enucleation of the prostate) and electroenucleation (mono- or bipolar) are highly effective and safe. They have been endorsed by the latest version of the European Association of Urology guidelines as an alternative to not only open adenomectomy but also transurethral resection of the prostate (EAU Guidelines on Treatment of Non-neurogenic Male LUTS 2018). Therefore, many urologists face the possibility of replacing the treatments of BPH. In this article, we analyze the history of EEP techniques, both their pros and cons and, what are they today - just a popular trend or a new standard procedure for the surgical treatment of BPH?

Relevance: Erectile dysfunction (ED) is a common condition. Pharmacological management of ED involves medications produced by chemical synthesis. Despite high efficiency, their use is often accompanied by some side effects. Considering this, herbal preparations with sufficient efficacy and greater safety have received much attention., Aim: To compare the efficacy and safety of two herbal preparations (EFFEX Tribulus and Tribestan) based on Tribulus Terrestris herb dry extract in patients with ED., Materials and Methods: A total of 173 patients were enrolled in the study, of whom 87 (group I) and 86 (group II) received EFFEX Tribulus and Tribestan, respectively. The mean age of patients was 42.2+/-11.5 years in group I and 42.8+/-11.2 years in group II. One hundred fifty two patients completed the study. The follow-up was 13 weeks (the herbal preparation dose was titrated at week five after the treatment initiation). The effectiveness of treatment was assessed on five follow-up visits using the IIEF, AMS, MSF, GAQ questionnaires, and a complex of diagnostic and laboratory studies., Results: At visit five compared to visit 1, the mean IIEF erectile function domain score increased by 5.7+/-4.6 and 5.2+/-4.3 points in group I and II, respectively. In both groups, all other IIEF domain scores demonstrated a statistically significant increase. The AMS scores decreased from 32.93+/-10.04 to 25.02+/-7.62 points in group I and 31.78+/-10.37 to 24.55+/-7.31 points in group II. The SMF scores increased from 22.36+/-4.85 to 27.16+/-4.80 points in group I and from 22.13+/-3.69 to 26.10+/-5.69 points in group II. Besides, the use of the herbal preparations was associated with a decrease in the serum cholesterol level, more pronounced with increasing patient age (correlation coefficient -0.06, p=0.41)., Conclusion: The herbal preparations EFFEX Tribulus and Tribestan have a similar efficacy and safety profiles.