Artificial Intelligence in Andrology: From Semen Analysis to Image Diagnostics.

Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such as machine learning, artificial neural networks, and deep learning, have shown great potential in andrology and reproductive medicine. AI-based tools are poised to become valuable assets with abilities to support and aid in diagnosing and treating male infertility, and in improving the accuracy of patient care. These automated, AI-based predictions may offer consistency and efficiency in terms of time and cost in infertility research and clinical management. In andrology and reproductive medicine, AI has been used for objective sperm, oocyte, and embryo selection, prediction of surgical outcomes, cost-effective assessment, development of robotic surgery, and clinical decision-making systems. In the future, better integration and implementation of AI into medicine will undoubtedly lead to pioneering evidence-based breakthroughs and the reshaping of andrology and reproductive medicine.

The Renaissance of Male Infertility Management in the Golden Age of Andrology.

Infertility affects nearly 186 million people worldwide and the male partner is the cause in about half of the cases. Meta-regression data indicate an unexplained decline in sperm concentration and total sperm count over the last four decades, with an increasing prevalence of male infertility. This suggests an urgent need to implement further basic and clinical research in Andrology. Andrology developed as a branch of urology, gynecology, endocrinology, and, dermatology. The first scientific journal devoted to andrological sciences was founded in 1969. Since then, despite great advancements, andrology has encountered several obstacles in its growth. In fact, for cultural reasons, the male partner has often been neglected in the diagnostic and therapeutic workup of the infertile couple. Furthermore, the development of assisted reproductive techniques (ART) has driven a strong impression that this biotechnology can overcome all forms of infertility, with a common belief that having a spermatozoon from a male partner (a sort of sperm donor) is all that is needed to achieve pregnancy. However, clinical practice has shown that the quality of the male gamete is important for a successful ART outcome. Furthermore, the safety of ART has been questioned because of the high prevalence of comorbidities in the offspring of ART conceptions compared to spontaneous conceptions. These issues have paved the way for more research and a greater understanding of the mechanisms of spermatogenesis and male infertility. Consequently, numerous discoveries have been made in the field of andrology, ranging from genetics to several "omics" technologies, oxidative stress and sperm DNA fragmentation, the sixth edition of the WHO manual, artificial intelligence, management of azoospermia, fertility in cancers survivors, artificial testis, 3D printing, gene engineering, stem cells therapy for spermatogenesis, and reconstructive microsurgery and seminal microbiome. Nevertheless, as many cases of male infertility remain idiopathic, further studies are required to improve the clinical management of infertile males. A multidisciplinary strategy involving both clinicians and scientists in basic, translational, and clinical research is the core principle that will allow andrology to overcome its limits and reach further goals. This state-of-the-art article aims to present a historical review of andrology, and, particularly, male infertility, from its "Middle Ages" to its "Renaissance", a golden age of andrology.

A Comprehensive Guide to Sperm Recovery in Infertile Men with Retrograde Ejaculation.

Retrograde ejaculation (RE) is a condition defined as the backward flow of the semen during ejaculation, and when present can result in male infertility. RE may be partial or complete, resulting in either low seminal volume or complete absence of the ejaculate (dry ejaculate). RE can result from anatomic, neurological or pharmacological conditions. The treatment approaches outlined are determined by the cause. Alkalinizing urinary pH with oral medications or by adding sperm wash media into the bladder prior to ejaculation may preserve the viability of the sperm. This article provides a step-by-step guide to diagnose RE and the optimal techniques to retrieve sperm.

Relevance of Leukocytospermia and Semen Culture and Its True Place in Diagnosing and Treating Male Infertility.

The current WHO 2010 manual for human semen analysis defines leukocytospermia as the presence of peroxidase-positive leukocytes at a concentration >1×106/mL of semen. Granular leukocytes when activated are capable of generating high levels of reactive oxygen species in semen resulting in oxidative stress. Oxidative stress has been correlated with poor sperm quality, increased level of sperm DNA fragmentation and low fertility potential. The presence of leukocytes and pathogens in the semen may be a sign of infection and/or localized inflammatory response in the male genital tract and the accessory glands. Common uro-pathogens including Chlamydia trachomatis, Ureaplasma urealyticum, Neisseria gonorrhoeae, Mycoplasma hominis, and Escherichia coli can cause epididymitis, epididymo-orchitis, or prostatitis. The relationship between leukocytospermia and infection is unclear. Therefore, we describe the pathogens responsible for male genital tract infections and their association with leukocytospermia. The review also examines the diagnostic tests available to identify seminal leukocytes. The role of leukocytospermia in male infertility and its management is also discussed.

A Global Survey of Reproductive Specialists to Determine the Clinical Utility of Oxidative Stress Testing and Antioxidant Use in Male Infertility.

PURPOSE: The use of antioxidants is common practice in the management of infertile patients. However, there are no established guidelines by professional societies on antioxidant use for male infertility. MATERIALS AND METHODS: Using an online survey, this study aimed to evaluate the practice pattern of reproductive specialists to determine the clinical utility of oxidative stress (OS) testing and antioxidant prescriptions to treat male infertility. RESULTS: Responses from 1,327 participants representing 6 continents, showed the largest participant representation being from Asia (46.8%). The majority of participants were attending physicians (59.6%), with 61.3% having more than 10 years of experience in the field of male infertility. Approximately two-thirds of clinicians (65.7%) participated in this survey did not order any diagnostic tests for OS. Sperm DNA fragmentation was the most common infertility test beyond a semen analysis that was prescribed to study oxidative stress-related dysfunctions (53.4%). OS was mainly tested in the presence of lifestyle risk factors (24.6%) or sperm abnormalities (16.3%). Interestingly, antioxidants were prescribed by 85.6% of clinicians, for a duration of 3 (43.7%) or 3-6 months (38.6%). A large variety of antioxidants and dietary supplements were prescribed, and scientific evidence were mostly considered to be modest to support their clinical use. Results were not influenced by the physician's age, geographic origin, experience or training in male infertility. CONCLUSIONS: This study is the largest online survey performed to date on this topic and demonstrates 1) a worldwide understanding of the importance of this therapeutic option, and 2) a widely prevalent use of antioxidants to treat male infertility. Finally, the necessity of evidence-based clinical practice guidelines from professional societies is highlighted.

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility.

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.

Double-blind, randomised, placebo-controlled trial on the effect of L-carnitine and L-acetylcarnitine on sperm parameters in men with idiopathic oligoasthenozoospermia.

Carnitine is essential for energy metabolism and spermatozoa maturation. Combining L-carnitine and L-acetylcarnitine with micronutrients has been investigated as a treatment for infertility in men. We evaluated the effects of a therapeutic formulation, Proxeed Plus, on sperm parameters in oligoasthenozoospermic men. This prospective, randomised, double-blind, placebo-controlled clinical trial involved 175 males (19-44 years) with idiopathic oligoasthenozoospermia who failed to impregnate their partners (12 months). Males received Proxeed Plus or placebo for 3 and 6 months. Sperm volume, progressive motility and vitality significantly (p < 0.001) improved after 6 months compared to baseline. Sperm DNA fragmentation index significantly decreased compared to baseline (p < 0.001) and the 3-month therapy (p = 0.014) in treated men. Increased seminal carnitine and α-glucosidase concentration also positively correlated with improved progressive motility. Decreased DNA fragmentation index was the good predictor of progressive sperm motility >10%, and simultaneous measurement of changes in sperm vitality and DNA fragmentation index gave the highest probability of sperm motility 10% (AUC = 0.924; 95% CI = 0.852-0.996; p < 0.001). Logistic regression analyses revealed DNA fragmentation index decrease as the only independent predictor of sperm motility 10% (OR = 1.106; p = 0.034). We have demonstrated the beneficial effects of carnitine derivatives on progressive motility, vitality and sperm DNA fragmentation. Combining metabolic and micronutritive factors is beneficial for male infertility.

Testis sparing surgery in the treatment of bilateral testicular germ cell tumors and solitary testicle tumors: A single institution experience.

BACKGROUND AND OBJECTIVE: To assess the oncologic and functional outcomes of testicular sparing surgery (TSS) based on a single institution experience. METHODS: Forty-one patients with bilateral and 3 patients with solitary testicle tumors were referred to our institution. The inclusion criteria for TSS were normal serum testosterone levels, and tumor size (<2 cm). Sperm analysis and hormone status evaluation were performed preoperatively and postoperatively. None of the patients underwent local radiation therapy following TSS for reasons of fertility preservation. RESULTS: A total of 26 TSS were performed in 24 patients. The median follow-up period was 51.0 months. Seven patients developed local recurrence, of which 5 had TIN and were subjected to radical orchiectomy, whereas re-do TSS was done in remaining 2 patients. The overall survival of the study group was 100%, and the presence of testicular intraepithelial neoplasia (TIN) was associated with worse recurrence-free survival (P=0.031, log-rank). Testosterone values were normal in all of the patients, while 4 patients achieved conception. CONCLUSIONS: TSS is acceptable from an oncological point of view, and it enables continuation of a patient's life without lifelong hormonal substitution. Additionally, local irradiation therapy could be delayed in patients with TIN who wish to father children, but with high local recurrence rate.

The correlation of biochemical and morphologic parameters in the assessment of sperm maturity.

OBJECTIVE: To examine the relationship between biochemical markers and morphologic sperm characteristics, including head, neck, and tail changes. METHODS: The study evaluated 154 patients who went to the Andrology Laboratory of the Clinic of Urology, Clinical Center of Serbia. Patients were divided into 4 groups: normozoospermic, oligozoospermic, severe oligozoospermic, and asthenozoospermic, according to the sperm concentration and motility. RESULTS: The differences in creatine kinase (CK) and CK-M levels between normozoospermic and the 2 groups of oligozoospermic patients were significantly different (P <.01). The CK and CK-M levels correlated negatively with sperm concentration and sperm motility, but correlated positively with the pathologic sperm form. Patients with CK values >0.093 have a total number of pathologic forms higher than 0.40 (87.5% sensitivity, 77.3% specificity, the area under the curve was 0.832, P <.001). Patients with CK values <0.09 U/L have normal spermatogenesis and pathologic disorder of the head <15%, neck <12%, and tail <10%. CONCLUSION: The relation between sperm morphology and biochemical markers included in the maturation process is established during the sperm genesis process. If the results of these markers are used together with the morphology of the spermatozoa in the interpretation of infertility, it would lead us to better insight of the fertility potential of the each patient.

Glycosaminoglycans in the urinary bladder mucosa, tumor tissue and mucosal tissue around tumor.

INTRODUCTION/AIM: Glycosaminoglycans (GAG) are one of the main constituents of the connective tissue and cellular membrane. Their presence has been evidenced in mucosa and muscular tissue of the urinary bladder of both healthy individuals and those affected by carcinoma. This suggest their potential role in the onset of bladder carcinoma and follow-up of those patients. The aim of the study was to determine GAG levels in tumor tissue and the surrounding bladder mucosa in patients with bladder tumor, as well as in the bladder mucosa in patients with bladder carcinoma, and to compare the results according to the grade and stage of tumor and relapse. METHODS: Tissue samples were taken in 61 patients (48 males and 13 females), mean age 61.5 years, range 40-92 years, obtained by transurethral resection (TUR) of bladder tumor, and 8 healthy persons. Determination of a total GAG content in the tissue samples was done by the Whiteman's method and then compared regarding the tumor grade and stage. RESULTS: Tumor grade and stage directly correlated with the levels of GAG. The GAG levels were significantly higher in tumor samples as compared to healthy mucosa. CONCLUSION: Higher GAG levels were recorded in all the patients with bladder tumors comparing to samples obtained from healthy individuals. GAG levels do not predict tumor relapse.

Isolated eyeball metastasis of non-seminomatous germ cell testicular tumor.

INTRODUCTION: Testicular tumors most frequently metastasize to regional lymph nodes. Non-seminomatous tumor metastasis of testicle (NSGCTT) to the eyeball is rare. CASE REPORT: We presented a 24-year old man, referred to the ophthalmologist due to acute pain and abrupt loss of sight in the left eye accompanied by its enlargement. Orbital and endocranial computerized tomography (CT) was carried out, indicating the tumor in the left eye. His previous medical history provided the information that the right testicle was painlessly enlarged for 8 months. Ultrasonography showed a completely tumorously altered testis. Abdominal and chest CT failed to reveal any secondary deposits in visceral organs and lymph glands. Tumor markers (AFP - alpha-fetoproteins, beta hCG - human choronic gonadotropin beta) were elevated. Right radical orchiactomy was performed (showed NSGCTT), followed by polychemotherapy with cisplatinum 100 mg/m2, etoposide 120 mg/m2, bleomycin 15 mg/m2 (PEB x 4), resulting in normalization of tumor marker values and significant regression of the left eyeball. Next, the left eye enucleation and ocular prosthesis implantation was carried out. Pathohistological evaluation indicated fibrosis and necrosis only. In a 5-year follow-up period, the patient was free of recurrence. CONCLUSION: Isolated hematogenous metastasis of the NSGCTT to the eye is rare. In our case, the left eye was the only metastatic localization. After chemotherapy and eye enucleation the patient was in a 4-year follow-up period free of the recurrence.

Modulation of aldosterone release by epidural analgesia impacts brain natriuretic peptide: a link to stress cardiomyopathy? Pilot study.

OBJECTIVE: Data pertaining to whether stress-induced aldosterone release is associated with cardiac disorders are lacking. This study was designed to compare whether the modulation of intra-operative aldosterone release by epidural analgesia had an effect on the brain natriuretic peptide (BNP) levels. DESIGN, PATIENTS, MEASUREMENTS: A study was pilot prospective, open label randomized one. Patients were randomized to one of two anaesthesia protocols: group 1 included 13 patients who received general anaesthesia, and group 2 included 12 patients who received combined general anaesthesia and epidural analgesia. Study protocol was by completed 25 male patients, median age 56 years, without significant comorbidities, who underwent radical cystectomy because of urinary bladder tumour. Serum aldosterone, BNP, cortisol (measured by radioimmunoassay), adrenocorticotropine hormone (ACTH) (by solid-phase ELSA), blood chemistry, complete blood count and vital signs were compared preoperatively, intra-operatively and at postoperative days (POD) 1 and 7. RESULTS: Hemodynamics was stable in both groups. Group 1 showed threefold serum aldosterone, (P = 0·001) 20-fold ACTH (P = 0·003) and twofold cortisol (P = 0·001) increases intra-operatively, unlike group 2. Both groups had a twofold BNP increase in POD 1 that remained above normal on POD 7 only in group 1 (P = 0·02; P = 0·019 vs group 2). CONCLUSION: Alleviation of aldosterone release by epidural analgesia modulated the postoperative serum BNP pattern in patients with a low risk for cardiac diseases who underwent noncardiac surgery.

Comparison of open nephroureterectomy and open conservative management of upper urinary tract transitional cell carcinoma.

INTRODUCTION: The treatment preserving the kidney for upper urinary tract (UUT) transitional cell carcinoma (TCC) is still controversial. We aimed to elucidate the results of open conservative surgery and compare them with the results of radical nephroureterectomy (RNU). PATIENTS AND METHODS: The study included 107 patients with UUT TCC treated by open conservative surgery (21 patients) or nephroureterectomy (86 patients). Epidemiological, clinical and pathological characteristics of patients as well as 5-year survival rates were compared between groups. RESULTS: Patients treated by conservative surgery had a significantly higher rate of bilateral tumors (38% vs. 3%, p = 0.0001) and smaller tumor size than those treated by radical operations (2.60 +/- 1.24 vs. 3.99 +/- 3.94 cm, p = 0.060). Five-year survival rates for patients treated by conservative and radical surgery were 59 and 55%, respectively. Within the group of patients treated by conservative surgery, 5-year overall survival rates of patients operated due to imperative and elective indications were 41 and 75%, respectively. In univariate analysis, RNU was a statistically significant predictor of poorer outcome of the disease in comparison with conservative surgery (HR = 2.2, 95% CI 1.1-4.6, p = 0.030). CONCLUSIONS: The mode of operation affects the outcome of UUT TCC patients, in addition to factors such as tumor grade, stage and size.

The treatment of stage A testicular seminoma by carboplatin monochemotherapy.

BACKGROUND/AIM: Although radiotherapy is considered to be a standard treatment of stage A testicular seminoma, an increasing number of studies have reported encouraging results of the treatment by carboplatin monochemotherapy (CBDCA). The aim of this study was to analyse the treatment results of patients with clinical stage A seminoma treated by CBDCA on daily basis in the period June 1999 to September 2008. METHODS: A total of 124 patients, mean age 36.63 years (20-62 years), with stage A testicular seminoma were treated, upon radical orchiectomy, by adjuvant CBDCA (400 mg/m2 on day 1 and 22). RESULTS: Chemotherapy was well tolerated, except moderate nausea on the day of the drug administration and the following day. No patient had any serious disorders in blood cells count requiring substitutional treatment. During the mean follow-up period of 37.5 (range 6-111) months, three relapses were noted (2.41%) and none neoplasm of contralateral testicle or any other organ. CONCLUSION: Simple and easy carboplatin administration with excellent treatment results, along with good tolerance and absence of comorbidity, poses itself as a new "gold standard" of treatment for stage A testicular seminoma.

Risk factors for treatment failure in renal suppurative infections.

There are conflicting results of published studies about prognostic value of various factors in purulent renal infections. The purpose of this study was to identify and quantify potential risk factors for early and late treatment failure in such infections. A retrospective review of 75 renal suppurative infections, at three tertiary Serbian Clinics of Urology, was conducted. We considered numerous potential risk factors in a multivariate analysis. This series was comprised of 49 women and 26 men, with mean age of 56.7 years. There were 38 and 37 patients who experienced successful and unfavorable early treatment outcome, respectively. Overall mortality rate was 9.3%. Comorbidity [odds ratio (OR) = 1.6], complex suppurative pathological findings (OR = 3.6), presence of Pseudomonas spp. (OR = 6.7), multiple bacterial strains (OR = 2.7), and positive culture itself (OR = 3.6) were the predictors of poor early prognosis. A urological intervention and presence of pyonephrosis significantly increased the chance for good initial outcome (OR = 0.32 and 0.37, respectively). In the late treatment failure analysis presence of comorbidities (OR = 5.8) and treatment complications (OR = 7.5) significantly increased chance for fatal outcome. Patients' baseline health status and complexity of suppuration itself were the most important predictors of clinical outcomes. Surgical drainage dominated over antimicrobial therapy.

Predictors of surgical site infection in dirty urological surgery.

OBJECTIVES: Risk factors for surgical site infection (SSI) following urologic dirty operations have not been clearly identified. This study was conducted to describe incidence, potential risk factors and common causative pathogens of the SSI in such operations. METHODS: Medical records of patients who had undergone simple nephrectomy or lumbotomy for suppurative renal infection at our institutions from 1999 to 2006 were retrospectively evaluated. The following data were retrieved: presence of SSI, demographic data, laboratory findings, comorbidities, microbiological data, type of renal suppuration, type of urological surgery and antibiotic regimen. Risk factors for SSI were evaluated using the multiple logistic regression model. RESULTS: Sixty-five patients (mean age 55.6 +/- 13.1 years) were eligible for data analysis. In 20 of them (30.8%) a SSI was identified. The most common isolated pathogens were gram-negative bacteria. At univariate logistic regression analysis risk factors significantly associated with SSI included: presence of emphysematous infection, hypoalbuminemia, number of predisposing conditions, emergency operations, isolation of Enterobacteriaceae, positive pus culture. The use of trimethoprim/sulfamethoxazole was associated with a decreased risk for SSI. Multiple logistic model identified only the emergency operations and isolated Enterobacteriaceae as independent predictors of SSI (odds ratio [OR] = 11.1) (95% confidence interval [CI] = 3.0-40.8) and OR = 3.9 (1.0-14.8), respectively. CONCLUSIONS: Patients with suppurative renal infections are submitted to life-saving emergency surgery. Urological surgeons should keep in mind that this carries a high risk for subsequent SSI. Effective preventive measures in these circumstance cannot be identified. Further research in this area is necessary to clarify this issue.

[Alport's syndrome and benign familial haematuria: light and electron microscopic studies of the kidney].

INTRODUCTION: Hereditary nephropathy is clinically characterized by the familial occurrence in successive generations of progressive haematuric nephritis and neural hearing loss. Hereditary nephropathy of Alport's syndrome (AS) and benign familial (recurrent) haematuria (BFH) are morphologically characterized by specific and diagnostically important thickening and splitting of lamina densa of the glomerular basement membranes. Those lesions can be recognized only by electron microscopy. Hereditary nephritis is usually present clinically with haematuria, and new mutations without a family history of haematuria. It is therefore important to differentiate hereditary nephritis from BFH and no familial haematuria. Thus, electron microscopy is essential in diagnosis of haematuria. OBJECTIVE: The aim of this study was to describe, by light microscopy, constellation of renal alterations by which hereditary nephropathy can be recognized with high probability as well as to compare the diagnostic validity of the findings observed by light and electron microscopy in AS and BFH. METHOD: We examined 48 renal biopsies of the patients with hereditary nephoropathies by light and electron microscopy. Tissue samples were fixed in buffered paraformaldehyde and embedded in paraffin for long-term preservation. For the electron microscopy analysis, the following fixation in 4% glutaraldehyde tissue was postfixed in 1% osmium tetroxide. Thereafter, the following dehydration procedure tissue slices were embedded in epon. RESULTS: Our results demonstrated that the interstitial foam cells, foetal-like glomeruli, minimal glomerular abnormalities with stain less intense in basement membranes, mild irregular mesangial widening, focal thickening of Bowman's capsule, foci of dilatation tubules, tubular ectasia and atrophy, erythrocyte tubules casts were present in hereditary nephritis. Additionally, light microscopic biopsy findings in patients with BFH were either normal or revealed minor changes (e.g. increased mesangial matrix). All biopsies were reevaluated by electron microscopy and ultrastructural findings confirmed the diagnosis of hereditary nephropathies. CONCLUSION: The findings observed by light microscopy represent an important step that leads to a definitive diagnosis of AS and BFH.The definitive diagnosis, however, depends on electron microscopy.

Survival of patients with transitional cell carcinoma of the ureter and renal pelvis in Balkan endemic nephropathy and non-endemic areas of Serbia.

OBJECTIVE: To evaluate the characteristics and survival of patients with upper urinary tract (UUT) transitional cell carcinoma (TCC) in Serbia, followed for >/=5 years or until death. PATIENTS AND METHODS: From 1998 to 2005 we analysed 114 cases of pathologically confirmed UUT TCC, divided into two groups according to topographical characteristics, and compared their demographic, clinical and pathological characteristics. The influence of various factors on overall 5-year survival of patients with UUT TCC was also tested. The prognostic value of different variables was assessed by univariate and multivariate Cox proportional-hazard models. RESULTS: The most important change in demographic characteristics of the patients with UUT TCC in Serbia was a similar proportion of patients residing in areas of Balkan endemic nephropathy (BEN) and non-endemic areas. The median (range) follow-up was 67 (46-88) months. The 5-year probability of survival was 51.2 +/- 5.8%. There was a significantly lower probability of 5-year survival for patients with a higher histological grade (P = 0.001), higher T stage (P < 0.001) and tumour size >3 cm (P = 0.001) at diagnosis. In this cohort of patients the independent predictors of a poorer outcome of the disease were being female (hazard ratio, HR, 2.2, P = 0.010), tumour size >3 cm (HR 2.8, P = 0.001) and T3 or T4 stages (HR 3.1, P = 0.001). CONCLUSION: Comparative analysis of the characteristics of UUT TCC between patients from BEN and non-endemic areas of Serbia showed similarities in demographic, clinical and pathological features. Factors that significantly influenced survival of patients with UUT TCC were being female, tumour size and tumour grade and stage.

[Pulsative hematoma--a penile fracture complication].

BACKGROUND: Fracture of the penis is a direct blunt trauma of the erect or semi-erect penis. It can be treated by conservative or surgical means. Retrospective analyses of conservative penile fracture treatment reveal frequent immediate and later complications. CASE REPORT: We presented a 41-year-old patient with pulsative hematoma caused by an unusual fracture of the penis. Fracture had appeared 40 days before the admittance during a sexual intercourse. The patient was treated surgically. CONCLUSION: Pulsative hematoma (pulsative diverticulum) is a very rare, early complication of a conservatively treated penile fracture. Surgical treatment has an advantage over surgical one, which was confirmed by our case report.

Glutathione S-transferase-P1 expression correlates with increased antioxidant capacity in transitional cell carcinoma of the urinary bladder.

OBJECTIVES: Our aim was to perform a comprehensive analysis of the antioxidant capacity of transitional cell carcinoma (TCC) of urinary bladder and discern the role of enzymes associated with glutathione (GSH) in maintaining high GSH levels in these tumours. Because the redox-sensitive protein glutathione S-transferase P1 (GSTP1) might provide an important link between high antioxidant capacity and inhibition of apoptotic pathways, we also explored how the redox state in tumour cells interacts with the expression of GSTP1. METHODS: We examined spectrophotometrically the specific activities of GSH-replenishing enzymes involved in GSH synthesis (gamma-glutamylcysteine synthetase, gamma-GCS), GSH regeneration (glutathione reductase, GR), and antioxidant protection (glutathione peroxidase, GPX; superoxide dismutase, SOD) in the cytosolic fraction of tumours and the surrounding normal tissue of 30 TCC patients. GSTP1-1 expression was also analyzed. RESULTS: We found a significant increase in the activity of both GSH-replenishing and antioxidant enzymes as well as enhanced GSTP1-1 expression in tumours in comparison with adjacent normal uroepithelium. Mean gamma-GCS and GR activities in tumours were about 4- and 2-fold higher, respectively, than in corresponding normal tissue. Expression of GSTP1 correlated significantly with GSH level and gamma-GCS and GR activities. GPX and SOD activities in TCC were also markedly increased. CONCLUSIONS: Enhanced GSH-replenishing pathways account for increased GSH levels in TCC. Upregulated GPX and SOD also contribute to high antioxidant potential in TCC. Under such conditions, expression of redox-sensitive GSTP1 protein is upregulated.