[Results of using the BESTFertil preparation in patients after microsurgical sub-groin varicocelectomy (Marmaras operation)].

INTRODUCTION: Up to 15% of couples around the world face the problem of infertility, while male factor in infertile marriages occurs in up to 50% of cases. Varicocele occurs in 15% of the male population and in 35% of men with infertility. For now, the only effective method of treating varicocele is operative. After surgical treatment, there is an improvement in spermogram parameters, however, it is not always possible to achieve normal value of each parameter. PURPOSE OF THE STUDY: To assess the efficiency of BESTFertil in patients after varicocelectomy. MATERIALS AND METHODS: The single-center, prospective, randomized study at the University Clinic of Urology, Russian National Research Medical University named after N.I. Pirogov was conducted comparing the postoperative parameters of patients who underwent varicocelectomy, followed by the course of BESTFertil (main group) and without it (control group). A total of 63 patients were included in the study: the main group - 33 patients and the control group - 30 patients. The inclusion criteria for the study were: the presence of varicocele as the cause of pathospermia and / or the absence of pregnancy in marriage for 12 months or more of regular sexual activity without contraception, in the absence of other organic pathology as a possible cause of infertility, age from 18 to 45 years. Patients from both groups underwent surgical treatment of varicocele - microsurgical subinguinal varicocelectomy according to the standard Marmar technique using an operative microscope. Patients from the main group received BESTFertil for 3 months according to the recommended scheme. RESULTS: In the main group an average increase in the volume of ejaculate in 6 months was 0.48 ml (11.2% of the initial), the increase in concentration was 24.4 mln / ml (59.1%), the increase in motility was 25.2% (69.2%), morphologically normal forms - 3.4% (106.3%). A relapse of the disease was revealed in one patient, according to ultrasound and angiography, however, there was also a positive dynamic of spermogram parameters: an increase in ejaculate volume - 0.8 ml; increase in sperm concentration - 22 mln/ml; A + B motility-32%; morphologically normal forms - 1%. Four patients (16.7% of the total number of patients with infertile marriage in the main group) reported pregnancy. In the control group, an average increase in the volume of ejaculate in 6 months was 0.07 ml (1.7% of the initial), the increase in concentration was 11.7 mln / ml (27%), the increase in motility was 10.6% (32.7%), morphologically normal forms - 0.6% (9.8%). Two patients (9.1% of the total number of patients with infertile marriage in the control group) report pregnancy after treatment. One patient had a relapse of the disease, confirmed by angiography, despite his spermogram parameters correspond to normospermia. CONCLUSIONS: These results allow us to conclude that the course of BESTFertil in patients after treatment of varicocele allows to achieve a clinically and statistically significant increase in spermogram indicators such as ejaculate volume, its concentration, sperm motility and the number of morphologically normal forms, which can help patients achieve natural pregnancy or resort to assisted reproductive technologies.

[Evaluation of the effectiveness of surgical treatment of recurrent urethral stricture].

INTRODUCTION: The recurrent course of the disease stricture is a complex problem for both the patient and the operating surgeon and requires an integrated approach to treatment only in expert centers. PURPOSE OF THE STUDY: To assess the effectiveness of methods of surgical treatment of recurrent urethral strictures. MATERIALS AND METHODS: At the University Clinic of Urology, Russian National Research Medical University named after N.I. Pirogov, an analysis of the results of surgical treatment of patients with recurrent urethral stricture from 2012 to 2020 was carried out. This work included patients who underwent surgical treatment for recurrent urethral stricture. A total of 120 men were involved in the work. The median length of the stricture was (min-max) - 2 (0.5-16 cm). In 95 (79.1%) patients, stricture of the bulbous urethra, in 15 (12.5%) - in the penile urethra, in 2 (1.7%) patients had panurethral stricture, in 6 (5.0%) - membranous urethra and in 2 (1.7%) - meatus. All patients were divided into two groups: with recurrent urethral stricture after primary DVIU (group I, n=77) and recurrent urethral stricture after primary urethroplasty (group II, n=43). Depending on the method of surgical treatment of recurrent urethral stricture, patients in group I were divided into 4 subgroups. Repeated DVIU + 3 months Autocatheterization - 16 (20.8%) patients; End-to-end urethroplasty - 37 (48.1%) patients; one-stage urethroplasty with a buccal graft or skin graft - 22 (28.6%) patients; multistage urethroplasty or perineostomy - 2 (2.5%) patients. Group II was also divided into 4 subgroups. DVIU - 17 (39.5%) patients; end-to-end urethroplasty - 6 (13.9%) patients; one-stage urethroplasty with a buccal graft or skin graft - 9 (20.9%) patients; multistage urethroplasty - 11 (16.7%) patients. Median Qmax - 4.68 ml/sec. Preoperative cystostomy was observed in 31 (25.8%) patients. RESULTS: The median follow-up was 24 months (range 12 to 76 months). Depending on the method of surgical treatment of recurrent urethral stricture, the effectiveness of DVIU according to strict indications was 75.7%. End-to-end urethroplasty showed an efficiency of -88,4%. One-stage augmentation urethroplasty had an efficiency of -77,4%, and multi-stage urethroplasty showed an efficiency of 84.6%. The IPSS value for the observation period 2 years was 2.6+/-0.9 points. The average value of Qmax at the time of observation was 19.4+/-7.1 ml/sec. The effectiveness of the treatment was 82%. During the follow-up period, a relapse was noted in 22 (18%) patients. The overall effectiveness of the treatment of recurrent urethral stricture, taking into account the treatment of recurrent cases of disease recurrence, was 97.5%. CONCLUSIONS: Urethroplasty is the treatment of choice for recurrent urethral strictures, which has been shown to be more effective than DVIU. However, the results of urethroplasty for recurrent strictures are worse than for primary strictures.

[Pathomorphological aspects of urethral strictures of various etiologies].

INTRODUCTION: The study of the structure of strictures of various etiologies is an open and uncertain issue of modern urology. AIM: To evaluate the morphological and immunohistochemical structure of strictures of various etiologies. MATERIALS AND METHODS: The study involved postoperative tissue of a pathologically altered urethra of 110 patients aged 23 to 74 years who underwent treatment at the University Clinic of Urology, Russian National Research Medical University. N.I. Pirogova (2014-2018) with Ds: urethral stricture. Morphological study: Van-Gieson staining; hemotoxylin - eosin. Immunohistochemical study: mouse monoclonal antibodies to muscle and connective tissue markers (Smooth Muscle Actin, Vimentin, Calponin) and inflammation markers (CD45R, CD58, CD138, CD20, CD3) were used as primary antibodies in all reactions. RESULTS: According to the revealed morphological changes, the material was divided into three groups: group I (n=27) - active inflammation; group II (n=33) - the predominant development of connective tissue with low activity of inflammation; group III (n=50) - mixed (chronic mild inflammation, an even amount of connective tissue). In a morphological study of idiopathic urethral strictures, it was noted that the multicolumnar epithelium was replaced by a multi-layer flat epithelium with a weakly pronounced keratinization. Inflammatory changes were mild, including the submucosal connective tissue and the spongy body. Spongiofibrosis is accompanied by a significant reduction in the vascular bed of both venous sinuses and arteries. The same changes were observed in the inflammatory genesis of urethral strictures. In the study of strictures with traumatic etiology, a restructuring of the cylindrical epithelium was observed. In cases with severe inflammation in the mucosa, the changes were atrophic-hyperplastic in nature with reactive cell atypia. CONCLUSION: urethral Strictures in men have a specific etiological factor, but the pathogenesis of urethral lesions can be divided into: post-traumatic and post-inflammatory.

[Assessment of the regenerative potential of platelet-rich plasma in urethroplasty in the experimental model].

INTRODUCTION: Reconstructive plastic surgery is the gold standard in the treatment of primary urethral strictures, but the effectiveness of these methods does not reach 100%. In cases of recurrent urethral strictures, the effectiveness of standard operations is lower than with primary strictures, which requires a search for methods to improve the results of surgical treatment. PURPOSE OF THE STUDY: To evaluate the structure of the intercellular matrix, the cellular composition and regenerative potential of a plasma enriched in platelets after performing urethroplasty on a biological model. MATERIALS AND METHODS: Experiment was carried out on male rabbits ("Burgundy" breed) weighting 3.0-4.5 kg (18 individuals). 18 animals were divided into two groups: an experimental one (contained 9 individuals) and a control one (contained 9 individuals). All animals in each group were subjected to end-to-end plastic surgery of the urethral bulbous region using standard procedures. In the control group 4 ml of 0.9% NaCl isotonic solution was injected along the perimeter of the suture into anastomotic zone of the spongy body. Autologous plasma was injected to the animals from the experimental group. Histopathological examination was made by using routine pathological assessment with hematoxylin-eosin staining. The study also assessed the distribution and orientation of collagen fibers with Van Gieson stain. In order to objectively detail inflammatory and regenerative changes an additional immunohistochemical analysis was performed for the following antibodie groups: CD79a, CD43, CD31 (PECAM1), MMP1, MMP9. Quantitative analysis of structural changes was carried out by counting B- and T-lymphocytes having a positive membrane reaction with CD79a and CD43, respectively, in 10 representative sites in view (HPF) with a lens aperture of 0.65 in the highest concentration areas ("hot spots"). The expression level of MMP1, MMP9 was estimated by counting positive cells in 10 representative sites in view with a lens aperture of 0.65 in the submucosal and muscle layers. The level of angiogenesis in micropreparations was evaluated by counting the number of vessels in 10 sites in view (objective aperture of 0.65), reliable endothelial visualization was performed using CD31 expression (PECAM1). RESULTS: In the analysis of histological material use of platelet-rich plasma in the suture zone helps to reduce the area of necrotic changes and the inflammation severity, accelerated migration of macrophage-histiocytic cells to the alteration site and increased blood supply due to enhanced angiogenesis. In experimental samples a higher expression of metalloproteinases (collagenases) types 1 and 9, decreased collagen production and the correct orientation of collagen fibers during repair processes were noticed. CONCLUSIONS: The use of platelet-rich plasma helps to accelerate the reparative processes in the spongy body after urethroplasty. Another important positive effect of platelet-rich plasma is an increase in the expression of metalloproteinases, which leads to a decrease in collagen production and the correct orientation of collagen fibers. This allows to reduce the amount of pathological fibro-scar tissue in the operation area.

[Iatrogenic urethral structures in men].

INTRODUCTION: Iatrogenic urethral damage is the leading etiologic factor for urethral stricture in men in developed countries and second after traumatic injury in developing ones. This study aimed to evaluate the frequency of iatrogenic strictures of the urethra and the results of their treatment. MATERIALS AND METHODS: This retrospective analysis comprised 133 patients who were treated for iatrogenic urethral stricture from 2011to 2016. Group I included 72 (54%) patients after trans(intra)urethral interventions (transurethral resection of the prostate or urinary bladder), urethral dilation, traumatic catheterization, etc. Forty-five (34%) patients with post-catheter strictures (ischemic/post-inflammatory), 7 (5%) patients after failed treatment of hypospadias, and 9 (7%) patients after open adenomectomy made up groups II, III, and IV. The diagnosis of recurrent stricture and the need for repeat surgical intervention were determined based on uroflowmetry, urethrography, and urethrocystoscopy. RESULTS: In group I, the mean extent (rank) of the stricture was 2 (0.1-15) cm, the most frequent location (85%) was the bulbar urethra. In group II, the most frequent location (71%) was also the bulbar urethra with a mean stricture length of 2.4 (0.3-13) cm. There were 4 cases of panurethral strictures, lesions of the penile urethra and meatal stenosis. In group III, the strictures were on average 6 (2-12) cm long. Patients group IV had strictures of the bulbar and prostatic urethra. In general, the effectiveness of endoscopic treatment (direct vision internal urethrotomy, DVIU) was 52%, the effectiveness of urethroplasty varied from 83 to 100% depending on the method. In group I, the effectiveness of the DVIU was 52%, various types of urethroplasty - 88-100%, in group II - 50% and 82-100%, respectively. In group III, the effectiveness of the single-stage/multi-stage buccal mucosa urethroplasty was estimated at 0%/100%. In group IV, the effectiveness of DVIU/urethroplasty/perineal prostatectomy was 20%/75%/100%. CONCLUSION: The proportion of iatrogenic urethral strictures in large megacities can reach 45%. Iatrogenic urethral strictures most commonly result from catheterization and transurethral interventions. Each subgroup of iatrogenic strictures is characterized by its location, extent and degree of urethral spongiofibrosis. With the correct choice of surgical modality, urethroplasty is almost twice more effective than DVIU.

[Surgical technique and the first clinical experience of augmentation urethroplasty without dividing of corpus spongiosum (KODAMA technique)].

AIM: In case of complex and long urethral stricture a use of augmentation technique is often limited by "critically" narrowing of urethral plate. In such cases, the augmentation anastomotic urethroplasty without division of the corpus spongiosum can be the method of choice, because it allows to perform simultaneous augmentation urethroplasty with maximal sparing of antegrade blood flow in corpus spongiosum. MATERIALS AND METHODS: In urologic clinic of N.I. Pirogov City Clinical Hospital No1 the analysis of 17 patients who were undergone to augmentation anastomotic urethroplasty without division of the corpus spongiosum (Kodama technique), performed by single surgeon from 2013 to 2017 yy was done. The meant stricture length was 3.75 cm (2-6). Penile, bulbar and panurethral stricture was found in 6 (35.3%), 7 (41.2%) and 4 (23.5%) cases, respectively. RESULTS: Technique efficiency was 88.2% and in 2 patients (11.8%) a stricture recurrence developed. The mean maximum flow rate before and after surgery were 5.4 and 23.1 ml/s, respectively (p<0.05). The mean catheterization time was 14 (7-30) days. There were no patients with de novo urinary incontinence and erectile dysfunction. CONCLUSION: The initial results of augmentation anastomotic urethroplasty without division of the corpus spongiosum showed high efficiency. To our opinion, the antegrade blood flow sparing makes it the method of choice in patients with long non-traumatic urethral stricture (without severe spongiofibrosis), good preoperative erectile function but isolated length of "critically" narrowing of the urethral lumen.

[PLGA mesh-collagen hybrid scaffold and tissue-engineered product in substitution urethroplasty: experimental validation].

Urethral strictures are a pressing issue in modern medicine. Substitution urethroplasty is considered one of the most effective treatment methods. However, despite the surgery showing good results, many problems remain unresolved, one being substitute material deficiency in extensive or recurrent strictures, as well as in cases requiring multistage surgeries, including those used to treat hypospadias. Graft removal also leaves the donor area prone to diseases and increases the length of surgery leading to a higher risk of intra- and postoperative complications. Tissue engineering (namely tissue-engineered products comprised of scaffolds and cells) may be a useful tool in dealing with these issues. The authors assessed the characteristics of a novel hybrid scaffold created from "reconstructed" collagen and a poly(lactic-co-glycolic acid) mesh. The resulting composite product showed good mechanical properties and functional performance. The hybrid scaffold was non-cytotoxic and provided an adequate base for cell adhesion and proliferation. Biodegradation resulted in the scaffold being replaced by urothelium and urethral mucosa. The newly formed tissues possessed adequate structural and functional properties. Only one rabbit out of 12 developed urethral stricture at the site of scaffold implantation. The above-mentioned facts suggest that the novel hybrid scaffold is a promising tissue-engineered product with potential implication in substitution urethroplasty.