[Clinical guidelines for male infertility: controversial issues and the need to reach interdisciplinary consensus].

A review of controversial issues about the terminology on male infertility and reproductive function, which is currently used, as well as proposals for updating clinical guidelines for the diagnosis and treatment of male infertility and men in infertile couples are presented in the article. An algorithm is described, the elements of which ensure referral of patients based on the possibility and timing of restoration of reproductive function, taking into account the reproductive health of a woman, as well as increasing the likelihood of successful treatment aimed at the birth of a healthy child.

[Language, cultural adaptation and validation of the OABSS (Overactive Bladder Symptom Score) questionnaire in patients with overactive bladder].

AIM: To perform language and cultural adaptation and validation of the OABSS (Overactive Bladder Symptom Score) questionnaire among patients with overactive bladder (OAB), proposed as an effective tool for assessing the severity of symptoms and the efficiency of treatment in clinics of the Russian Federation. MATERIALS AND METHODS: In accordance with the protocols for carrying out such studies, the procedure of standardized forward-backward translation of the OABSS questionnaire was performed. Further, the intermediate Russian-language version was applied to 15 patients with subsequent correction of deficiencies and approval of the final Russian-language version of the questionnaire. In total, the study group included 176 patients of both sexes with OAB symptoms who filled out the questionnaire twice (test-retest) with an interval of 10-14 days. RESULTS: Based on the statistical analysis (Cronbach's alpha = 0.961), there was a significant degree of internal consistency of the sample. This fact is also supported by the very high retest reliability of the questionnaire (ICC >0.9). CONCLUSION: Our data showed that the Russian version of the OABSS questionnaire is a reliable and valid tool for subjective assessment of the severity of OAB symptoms.

[The features of pathogenesis of urolithiasis in patients with diabetes mellitus type 2].

INTRODUCTION: In recent years, a large number of studies has been published that proved a very significant role of diabetes mellitus type 2 for development of urolithiasis. The aim of our work was to conduct a comparative study of biochemical parameters of blood and urine as well as chemical composition of urinary stones in urolithiasis patients in the general population and in patients with diabetes mellitus type 2. MATERIALS AND METHODS: The work was divided into 2 stages. During the first stage an analysis of chemical composition of urinary stones in the general population (n=5669) and in patients with diabetes mellitus type 2 was carried out (n=350). During the second stage an analysis of biochemical parameters of blood and urine in urolithiasis patients in the general population (n=101) and in patients with diabetes mellitus type 2 was conducted (n=350). RESULTS: In the general population calcium oxalate stones was predominated (56.8%), while phosphate (24.9%) and urate (17.4%) stones were less frequent. In a subgroup of patients with diabetes mellitus type 2 uric acid stones were predominated (74.3%), significantly exceeding calcium oxalate (15.1%) and calcium phosphate (10.6%) stones. In the general population of patients with urolithiasis, hypercalciuria, hyperuricosuria, hyperuricemia and hypomagnesiuria was detected in 60.4%, 42.6%, 26.7% and 43.5% of cases, respectively. In patients with concomitant diabetes mellitus type 2, hypercalciuria, hyperuricosuria, hyperuricemia was observed in 9.4%, 26.7% and 42.5%, respectively. In 60.3% of patients with diabetes mellitus type 2 marked acidity of the morning urine was detected (pH<6.0). CONCLUSION: Correction of metabolic disorders in patients with urinary stone disease and diabetes mellitus type 2 should be aimed at increasing of urine pH and reducing the level of uric acid in the blood and urine.

[Use of buccal graft for the management of ureteral strictures].

This review analyses of the results of using buccal mucosa graft for the management of ureteral strictures. The authors identified sixteen original studies presenting the results of ureteral reconstruction using buccal grafts. Of them, twelve, three and one studies used the open, robotic and laparoscopic technique, respectively. Open surgery was performed 44 times in 42 patients (2 patients underwent bilateral ureteroplasty) with an average ureteral stricture length of 6.0 (2.5-11) cm. Ureteral patency was restored in 93.2% (41/44) of patients with an average follow-up of 26 (3-85) months. The robotic technique was used in 18 patients with an average ureteral stricture length of 3.25 (1.5-6) cm. Positive results after similar operations were achieved in 88.9% (16/18) of patients with an average follow-up of 15 (4-30) months. The laparoscopic technique was used only once for a ureteral stricture measuring 3 cm in length and was characterized as successful at a follow-up of 9 months. All surgical modalities were associated with minimal risk of early and late postoperative complications. The review results suggest that buccal substitution ureteroplasty can be regarded as an advantageous alternative to more complicated surgical procedures associated with greater complication rates (ileal ureteral substitution and kidney autotransplantation) used for long ureteral strictures.

[Imidafenacin for treatment of overactive bladder and urgent urinary incontinence: the results of open-label multicenter randomized controlled clinical trial].

INTRODUCTION: The analysis of the results of a multicenter, open, randomized comparative phase III clinical trial on the use of imidafenacin for treating patients with OAB was carried out. A clinical study was conducted according to GCP standards in 12 urological centers of the Russian Federation with the support of company AO "R-Pharm". MATERIALS AND METHODS: A total of 296 patients (men and women) aged from 18 to 65 years with OAB and urgent urinary incontinence were included in the study. All patients were randomized into two groups. In Group 1 (n=148) patients received -cholinoblocker imidafenacin 1 tablet (0,1 mg) twice a day. Group 2 patients (n=148) were prescribed a comparison drug tolterodine 1 tablet (2 mg) twice a day, as well. The duration of treatment was 12 weeks. RESULTS: The analysis of results showed a significant decrease in the OAB symptoms in both groups. In Group 1 a decrease of episodes of urge urinary incontinence was more pronounce compared to Group 2, as well as amount of day-time and night-time of episodes of urge urinary incontinence by the 2nd, 4th, 8th and 12th weeks of treatment in comparison with baseline scores. There were no differences between two groups in the severity of reducing average urinary frequency per day. Reducing the severity of urinary disturbances in patients of both groups was accompanied by an improvement in the quality of life. There was a significant and similar decrease in the average total score of both OAB Awareness Tool and EQ-5D questionnaires. Tolerability of treatment was satisfactory in both groups and there were no differences in the adverse events in Group 1 and 2. CONCLUSION: Imidafenacin showed high clinical efficacy for treating patients with OAB, which is not inferior, and in some values, is superior in comparison to tolterodine. Both drugs had a similar safety and tolerability profile.

[Laser therapy for male infertility. Part 1. Etiology and pathogenesis. experimental studies].

Male infertility is associated with a wide range of pathological conditions affecting both the sexual and other body systems: endocrine, nervous, blood, and immune. Laser therapy is a form of modern physiotherapy that applies low-intensity laser radiation in various parts of the body. It is widely used in all areas of modern medicine due to its high efficiency, ease of use, the absence of contraindications and side effects. The authors reviewed the results of 171 studies investigating laser therapy, of which 93 were experimental (20 in Russian and 73 international publications), 4 clinical and experimental (all in Russian), 74 clinical (73 in Russian and 1in English). Along with domestic literature, publications in Russian from Belarus, Georgia, Kyrgyzstan, Uzbekistan and Ukraine were studied. The article analyzes the experimental studies, somehow related to the problem of infertility and its treatment using low-intensity lasers. The analysis findings suggest that there are all prerequisites to develop a laser therapy as an effective modality for treating infertile men.

[Early diagnosis of risk for developing calcium oxalate urolithiasis].

AIM: To identify risk groups for calcium oxalate urolithiasis among healthy individuals and patients with urolithiasis in the Russian population using molecular genetics. MATERIALS AND METHODS: The study comprised 72 patients with calcium oxalate urolithiasis (study group) and 189 healthy adults from the general Russian population (control group). The study group consisted of 39 (54.2%) men and 33 (45.8%) women. The mean age of urolithiasis patients was 41.5+/-12.4 years. Analysis of polymorphic variants of 8 candidate urolithiasis genes: tumor necrosis factor 11B (TNFRSF11B, rs3134057), -subunit of the nuclear estrogen receptor (ESR1, rs851982), Cloto gene (KL, rs526906), vitamin D receptor (VDR, rs1540339 ), an extracellular calcium-sensing receptor (CASR, rs2202127), membrane anion transporter family 26 (SLC26A6, rs2310996), tumor necrosis factor 11 (TNFSF11, rs9525641), the calcium release-activated calcium modulator 1 (ORAI1, rs7135617) in two groups was performed by real-time PCR using Applied Biosystems test. Statistical analysis was performed using Fishers angular transformation and 2. RESULTS: In the polymorphism of the ORAI1 gene (rs7135617), the differences in the frequencies of the GG genotype and the G allele in the control sample and in the sample of patients with calcium oxalate urolithiasis were significant: p=0.0004 and p=0.001, respectively. No statistically significant differences in the genotype and allele frequencies were found in the remaining seven gene polymorphisms. CONCLUSIONS: Healthy individuals and patients with urolithiasis in the Russian population who have the GG genotype and/or the G allele of the polymorphism of the ORAI1 gene (rs7135617) represent risk groups for the formation of calcium oxalate stones.

[Laser therapy for mens infertility. Part 2. Systematic review of clinical trials].

Male infertility is a multifactorial syndrome associated with a wide range of pathological conditions affecting both the sexual and other body systems: endocrine, nervous, blood, and immune. Laser therapy is a form of modern physiotherapy that applies low-intensity laser irradiation (LILI) in various parts of the body. It is widely used in all areas of modern medicine due to its high efficiency, ease of use, the absence of contraindications and side effects. The authors reviewed the results of 171 studies investigating laser therapy, of which 93 were experimental (20 in Russian and 73 international publications), four clinical and experimental (all in Russian), 74 clinical (73 in Russian and 1 in English).Along with domestic literature, publications in Russian from Belarus, Georgia, Kyrgyzstan, Uzbekistan, and Ukraine were also reviewed. The review suggests that laser therapy should be used as much as possible in the management of male infertility not just due to high effectiveness, but also because of the lack of alternatives. For local application, optimal laser irradiation regimens are pulsed LILI of red (635 nm) and infrared (904 nm) spectra. For intravenous laser blood irradiation, the authors recommend alternating a continuous LILI with a wavelength of 635 nm (red spectrum) and 365 nm (ultraviolet spectrum).

5-Aminolevulinic acid in intraoperative photodynamic therapy of bladder cancer (results of multicenter trial).

The results of multicenter prospective trial for efficacy of combined modality treatment: transurethral resection (TUR)+photodynamic therapy (PDT) with alasens for bladder cancer are represented in the article. Trials were organized by Research Institute of Organic Intermediates and Dyes and conducted according to clinical protocol approved by Ministry of Health of Russia, at the sites of leading Russian cancer clinical centers. The trial included 45 subjects with verified diagnosis of non-muscle-invasive bladder cancer. Patients underwent TUR of bladder with simultaneous PDT as anti-relapse treatment. Alasens was administered to patients as intravesicular instillation of 3% solution in volume of 50ml with 1.5-2h exposure (prior to TUR). TUR was performed after instillation. PDT session was conducted immediately after the completion of TUR on a single occasion by means of combined local irradiation on tumor bed with diffuse irradiation on whole urinary bladder mucosa (light dose of local irradiation - 100J/cm2, diffuse irradiation - 20J/cm2). Good tolerance of the treatment was noticed, there were no complications. Among 45 patients included in the trial, 35 (78%) completed 12 month protocol follow-up without relapse. In our study PDT with alasens after TUR reported a recurrence rate of non-muscle-invasive bladder cancer for 1st year after treatment of 22%. TUR with intraoperative PDT with 5-aminolevulinic acid may offer an alternative in the treatment of non-muscle-invasive intermediate and high-risk bladder cancer.

[The incidence of acute urinary retention as an indicator of the quality of care for patients with benign prostatic hyperplasia].

AIM: To evaluate the incidence of acute urinary retention as an indicator of the quality of care for patients with benign prostatic hyperplasia by the example of "Urology" Program implemented in the Voronezh region. MATERIALS AND METHODS: As part of the program "Urology", the incidence of AUR was used as an indicator of quality of care for patients with BPH. Urological health care for patients with BPH was provided within a three-stage model. For each of the stages standardized packages of detailed methodological materials, including regional standards were developed. RESULTS: Over the 3 years of the program (2011-2013) questionnaire survey was conducted among 762 937 men 50-75 years old with 85.3-88.1% annual coverage of respondents. Over the past three years (2009-2012) there was consistent and statistically significant (p<0.05) decrease (from 11.27 to 1.5%) in the proportion of hospitalizations for AUR reaching a "plateau" (p>0.05) in 2012-2013. There was a significant correlation of AUR with the main indicators of effectiveness of BPH treatment: the structure of morbidity (prevalence of early BPH forms - groups 1 and 2), the number of surgical interventions, the frequency of complications (including surgical), general and specific costs for diagnosis and treatment of BPH. CONCLUSIONS: Acute urinary retention may be regarded as an integral indicator of the quality of care for patients with BPH.

[Genetic risk factors for recurrence-free urolithiasis in the russian population].

PURPOSE: Search for and identification of possible associations of recurrence-free urolithiasis with polymorphisms of urolithiasis candidate genes in the Russian population. MATERIALS AND METHODS: The study involved 43 patients with recurrence-free urolithiasis, 13 (30.2%) women and 30 (69.8%) of men (main group) from Central Russia, and 189 healthy adults (control group) from the same region. The mean age of the main group was 42.5+/-13 years. The venous blood samples were used for the evaluation. Real-time PCR using the "Applied Biosystems" test systems was performed to determine the spectrum and frequency of eight urolithiasis candidate genes polymorphisms: tumor necrosis factor receptor gene (TNFRSF11B (rs3134057), vitamin D receptor gene (VDR, (rs1540339), extracellular calcium-sensing receptor gene (CASR, (rs2202127), calcium release-activatedcalcium modulator 1 gene (ORAI1, rs7135617), Klotho gene (KL, rs526906), nuclear estrogen receptor alpha-subunit gene (ESR1, rs851982), tumor necrosis factor 11 gene (TNFSF11, rs9525641), and 26 gene family anionic membrane transporter gene (SLC26A6, rs2310996). Fishers angular transformation and 2 test were used for statistical analysis of the data. RESULTS: For ORAI1 gene, differences in genotype and allele frequencies in the control and main groups are significant: p=0.0001 and p=0.013, respectively. For polymorphisms of the other seven genes studied, the differences in genotype and allele frequencies are non-significant. The results indicate the presence of the association between recurrence-free urolithiasis and calcium release-activatedcalcium modulator 1 gene polymorphism (ORAI1, rs7135617), both in genotypes and alleles. CONCLUSIONS: In Russian population, genetic factors, in particular, ORAI1 (rs7135617) gene polymorphism, can play the role in the development of recurrence-free urolithiasis.

[Markers for non-invasive molecular genetic diagnosis of oncourological diseases].

Currently, there is accumulated mass of data on the molecular-genetic disorders in prostate cancer (PCa), bladder cancer (BC) and renal cancer (RC). Tumor cells in these diseases are present in the urine sediment; their number is sufficient for molecular genetic analysis that makes possible the development of noninvasive diagnosis of oncourological diseases. A characteristic feature of PCa includes the overexpression of the PCA3 gene; assay kit Progensa™ to quantify such overexpression has been developed; approximately 50% of tumors express a TMPRSS2-ERG chimeric oncogene. Combined analysis of PCA3 and TMPRSS2-ERG allows to detect PCa with a diagnostic accuracy of 84%, which is significantly higher than that of prostate specific antigen test. As a potential markers of BC, there are somatic mutations in FGFR3, PIK3CA, TERT genes in urine sediment, which are found in this disease with a frequency of about 60, 30 and 50%, respectively. The basis of the test system for DNA diagnosis of BC in urine sediment may include a definition of a combination of mutations in these genes with microsatellite instability. Aberrant methylation of the 5'-regulatory regions of tumor suppressor genes, integrated in the panel, also is considered as a tool in the diagnosis of RC (VHL, RASSF1, RARB2, CDH1), PCa (GSTP1, PTGS2, LGALS3) and BC (RASSF1, APC, SFRP2) after standardization of panels of loci investigated, sample preparation methods, bisulfite conversion, and the design of primers and probes. Thus, a test systems for molecular genetic diagnosis of oncourological diseases in urine sediment are currently available or may be developed in the near future.

[Methods of increasing the effectiveness of radical prostatectomy].

In search of ways to improve the results of radical surgical treatment of patients with prostatic cancer (PC), we analysed the results of examination and treatment of 130 patients with local PC performed in 2000-2010 years. All the patients have undergone retropubic radical prostatectomy (RPE). Of them, 25.4% received neoadjuvant hormonal therapy. Follow-up median was 53 months (16-122 months). We also estimated direct and indirect costs of RPE. Erectile dysfunction after RPE was registered in 93.1% patients, urinary incontinence--in 20% patients, anastomosis stricture--in 22.6%. Five and 10 year recurrence-free survival was 80 and 72%, respectively. Total (direct and indirect) costs of one PC patient's surgical treatment (RPE) reached 140891,29 roubles. Our calculations show that certain measures taken in practical activity of the urologists can reduce direct costs by about 25%. Thus, our study demonstrates that it is possible to avoid unjustified expenses and achieve good outcomes in surgical treatment of PC.

[A comparative clinical randomized trial of cernilton efficacy and safety in patients with chronic abacterial prostatitis].

The trial of efficacy and safety of two doses of the drug cernilton in patients with chronic abacterial prostatitis made in the Research Institute of Urology and I.M. Sechenov Medical Academy in 2008 gave evidence for subjective (NIH-CPSI, Sex-4, IPSS and other scales, QOL) and objective (leucocyte count in prostatic secretion) pronounced anti-inflammatory effects of the drug which persist for at least 6 months. Comparison of the two doses of cernilton showed significant differences in subjective response of the patients (NIH-CPSI and Symptom Frequency Scale). Cernilton is recommended as a medication of choice for treatment of patients with chronic abacterial prostatitis.

[Experience with application of ALMGP-01 device for local transrectal microwave hyperthermia of the prostate in the treatment of chronic prostatitis].

The article presents the results of a clinical trial of efficacy of ALMGP-01 device in 34 patients with chronic prostatitis. The device provides local microwave hyperthermia of the prostate which appeared highly effective in combined treatment of chronic prostatitis.

[Results of three-year clinical study of prostamol uno efficacy and safety in patients with initial symptoms of prostatic adenoma and risk of its progression].

Prostamol Uno (PU) efficacy and safety were studied in a multicenter, open-population, randomized and comparative trial. PU was given in a single daily dose 320 mg for 36 months to 50 patients with initial symptoms of prostatic adenoma (PA) in comparison with 50 matched controls. The trial evaluated PU action on the symptoms progression and quality of life with application of questionnaires IPSS and QoL (BS). It was found that PU treatment relieved PA symptoms by IPSS, while these symptoms progressed in the controls. QoL improved in the study group and deteriorated in the control one. Administration of PU significantly increased urinary flow rate though in the controls urinary flow rate decreased, size of the prostate diminished and increased, respectively. Changes in the PSA were not seen and were insignificant, respectively. The results of the study say that prostamol Uno in a dose 320 mg/day can prevent PA progression without side effects.