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Bladder cancer represents a major health issue. Transurethral resection is the first line treatment and an accurate assessment of tumor margins might warrant complete tumor removal. Genomic instability and proliferative potential are common hallmarks of cancer cells. We have previously demonstrated the utility of intraoperative flow cytometry (iFC), a next-generation margin evaluation methodology for assessment of DNA content, in the detection of several types of malignancy. In the current study we investigated the possible value of iFC in the characterization of bladder cancer during surgery. Samples from a population of 52 people with urothelial cancer were included in the study. The total time for iFC evaluation is 3–5 min per sample and included a two-step analysis, including DNA-index and Tumor-index calculation. First, DNA-index calculation revealed 24 hyperploid and one hypoploid tumor. Second, cell cycle analysis and Tumor-index calculation revealed that tumor samples are distinguished from normal cells based on their significantly higher proliferative potential. The standard for iFC evaluation was pathology assessment and revealed that our protocol exhibits an accuracy of 98% in defining the presence of cancer cells in a given sample. Our results support the further assessment of iFC value towards its use as a novel malignancy evaluation tool in transurethral resections.

To evaluate the potential of prostate cancer detection on the basis of prostate-specific antigen (PSA)-level and percent free PSA (% fPSA) according to the outcome of prostate needle biopsy.This was a retrospective study of 1040 patients that underwent a prostate biopsy in the Urologic Clinic of the University Hospital of Ioannina, Greece. The patients underwent needle biopsy after abnormal finding in digital rectal examination (DRE). Tissue samples were extracted using a 12-core TRUS-GB. The patients were divided into four groups according to the biopsy outcome. Total serum and free PSA were measured.The mean PSA concentration of cancer versus noncancer groups was significantly higher (p0.05). The positive predictive value (PPV) of PSA for serum concentration10 ng/ml was 47% while the negative predictive value (NPV) in patients with PSA levels4 ng/ml was 81%. The diagnostic accuracy of % fPSA for patients with PSA level between 4-10 ng/ml was 0.651 (95% CI, 0.549-0.754) (p0.05). A statistically significant difference in mean PSA concentration was recorded between prostate cancers classified as grade 2 (3+4=7) and 3 (4+3=7) and grade 4 (8) and 5 (9-10) (p0.05).Though informative and suggestive, PSA and % fPSA are not definitive for cancer or non-cancer determination. The differentiation of PSA level between tumours classified as grade 2 (3+4=7) and grade 3 (4+3=7) could support the determination of treatment by backing pathologist's interpretation of the histological diagnosis.

Background. Cisplatin (cis-diamminedichloroplatinum) is a widely used chemotherapeutic agent for the treatment of various cancers. Although it represents an effective regimen, its application is accompanied by side effects to normal tissues, especially to the kidneys. Cisplatin generates free radicals and impairs the function of antioxidant enzymes. Modulation of cisplatin-induced oxidative stress by specific antioxidant molecules represents an attractive approach to minimize side effects. Methods. We studied the ability of curcumin to sensitize leiomyosarcoma (LMS) cells to cisplatin. Assays for cell proliferation, mitochondrial function, induction of apoptosis, and cell cycle arrest were performed using various concentrations of cisplatin and a concentration of curcumin that caused a nonsignificant reduction in cell viability. Moreover, the effect of curcumin was examined against cisplatin-induced experimental nephrotoxicity. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen (BUN), and the kidney’s relative weight. Oxidative stress was measured by means of enzymatic activities of superoxide dismutase and glutathione peroxidase in the rats’ blood and malondialdehyde levels in rats’ urine. Results. In our study, we found that curcumin sensitizes LMS cells to cisplatin by enhancing apoptosis and impairing mitochondrial function. In an in vivo model of cisplatin-induced experimental nephrotoxicity, intraperitoneal administration of curcumin failed to preserve blood’s antioxidant enzyme activity and decrease lipid peroxidation. Nevertheless, curcumin was able to protect nephrons’ histology from cisplatin’s toxic effect. Conclusion. Our results showed that curcumin can act as chemosensitizer, but its role as an adjunctive cisplatin-induced oxidative stress inhibitor requires further dose-finding studies to maximize the effectiveness of chemotherapy.

Prostate specific antigen (PSA) is the most widely known screening test to detect prostate cancer (PCa). However, PSA testing has been recently put under the microscope mainly due to its weak correlation with prostate malignancy. In several clinical trials the PSA-screening validity for the diagnosis of PCa was evaluated. PSA lacks the ability to define the progression potential of the disease usually resulting in overdiagnosis and overtreatment of patients. Therefore, the development of new "multivariate" prediction models for PCa that would combine the PSA screening marker (and probably PSA metrics) with better biomarkers and imaging techniques has become an evolving field. New screening tests and/or methods with increased specificity could reduce the number of men undergoing prostate biopsy - thus alleviating patients from the anxiety and the distress experienced by an unnecessary (negative) biopsy- and minimizes the healthcare cost. Herein, we reviewed the information on PSA and other novel tests that can assist in diagnosing clinically meaningful prostate cancer.

Multiple sclerosis (MS) is the commonest progressive neurological disease affecting young people. With advancing disease, management of neurogenic detrusor overactivity (NDO) based on antimuscarinics may prove inadequate and if based on botulinum toxin, may necessitate clean intermittent self-catheterization. The aim of the study was to evaluate the effectiveness of combined mirabegron and desmopressin administration in the treatment of NDO in patients with MS.Sixty patients diagnosed with MS and NDO were evaluated. All had received treatment with solifenacin 10 mg/daily for 3 months and were displeased with the results. Patients were divided in four groups. In Group A (n = 15) patients continued receiving solifenacin 10 mg/daily; in Group B (n = 15) patients received mirabegron 50 mg/daily; in Group C (n = 15) patients received desmopressin 120 mcg/daily and in Group D (n = 15) patients received mirabegron 50 mg/daily and desmopressin 120 mcg/daily. All patients were assessed with a 3 day bladder diary at the beginning and at the end of the treatment.All patients in Groups A, B and C did not demonstrate statistically significant changes at the end of the treatment period in their 3 day bladder diary and in the presence of urinary infections. In Group D, a statistically significant improvement was noted in the mean change from baseline to end of treatment in micturition episodes (3.5 +/- 0.4 micturition/24h), in urgency episodes (2.3 +/- 0.2) and mean number of urinary incontinence (1.0 +/- 0.2 episodes/24h).Treatment with mirabegron and desmopressin revealed both effectiveness and safety in patients with NDO and MS.

Objective The objective of this study was to assess the accuracy of multidetector computed tomography (CT) in diagnosing perinephric (PN) and/or renal sinus (RS) fat invasion in patients with renal cell carcinoma (RCC), with reference to the CT findings predictive for the diagnosis of invasion. Methods This was a retrospective study of 48 RCCs. Examinations were performed on a 16-row CT scanner, including unenhanced and 3-phase contrast-enhanced CT scanning. Unenhanced transverse images and multiplanar reformations of each contrast-enhanced CT phase were evaluated. The predictive value of CT findings in diagnosing PN and/or RS fat invasion was determined using multivariate logistic regression analysis. Results The CT findings that were most predictive for the diagnosis of PN fat invasion were the presence of contrast-enhancing nodules in the PN fat and tumoral margins. Invasion of the pelvicaliceal system was the most significant predictor in the diagnosis of RS fat invasion. Conclusions Multidetector CT provides satisfactory results in detecting PN and/or RS fat invasion in RCC.

We evaluated the effects of vardenafil on testicular androgen-binding protein secretion (ABP). Bilaterally obstructed azoospermic (OA)-men (n = 19) (group A) underwent unilateral testicular biopsy. A group of nonobstructed azoospermic (NOA)-men (n = 68) (group B) underwent bilateral testicular biopsy. ABP secretion in vitro by testicular tissue was assessed in each participant of every group. In addition, intracytoplasmic sperm injection (ICSI) cycles were performed in several couples of group A or group B using frozen/thawed spermatozoa from the biopsy material. Ten OA-men (group A1), 14 NOA-men (group B1), and nine different NOA-men (group B2) had been positive for spermatozoa in the biopsy but pregnancies were not achieved in the respective female partners. Men of groups A1, B1 and B2 were treated with vardenafil, vardenafil and L-carnitine respectively. Then, the men of groups A1, B1 and B2 underwent a second testicular (unilateral) biopsy. Within the group A1 and within the group B1, ABP secretion rate was significantly larger after vardenafil treatment than prior to vardenafil treatment. In addition, fertilisation rates in ICSI cycles within groups A1 or B1 were not affected by vardenafil administration. Vardenafil administration in NOA-men increased ABP secretion and did not affect detrimentally the presence of testicular foci of advanced spermatogenesis.

The aim was to determine the magnetization transfer ratio (MTR) of normal testes, possible variations with age and to assess the feasibility of MTR in characterizing various testicular lesions. Eighty-six men were included. A three-dimensional gradient-echo MT sequence was performed, with/without an on-resonance binomial prepulse. MTR was calculated as: (SIo-SIm)/(SIo) × 100 %, where SIm and SIo refers to signal intensities with and without the saturation pulse, respectively. Subjects were classified as: group 1, 20-39 years; group 2, 40-65 years; and group 3, older than 65 years of age. Analysis of variance (ANOVA) followed by the least significant difference test was used to assess variations of MTR with age. Comparison between the MTR of normal testis, malignant and benign testicular lesions was performed using independent-samples t testing. ANOVA revealed differences of MTR between age groups (F = 7.51, P = 0.001). Significant differences between groups 1, 2 (P = 0.011) and 1, 3 (P

The aim of this study is to improve detection of testicular intraepithelial neoplasia (TIN) by measurement of apparent diffusion coefficient (ADC) values.Fifty-six MRI examinations of the scrotum, including 26 histologically proven testicular germ cell neoplasms were retrospectively evaluated. DWI was performed using a single shot, multi-slice spin-echo planar diffusion pulse sequence and b-values of 0 and 900 s mm(-2). ADC measurements were classified into three groups according to their location: group 1 (n=19), non-tumoral part, adjacent to testicular carcinoma, where the possible location of TIN was; group 2 (n=26), testicular carcinoma; and group 3 (n=60), normal testicular parenchyma. Analysis of variance (ANOVA) followed by post hoc analysis (Dunnett T3) was used for statistical purposes.The mean±s.d. of ADC values (×10(-3) mm(2)/s) of different groups were: group 1, 1.08±0.20; group 2, 0.72±0.27; and group 3, 1.11±0.14. ANOVA revealed differences of mean ADC between groups (F=38.859, P0.001). Post hoc analysis showed differences between groups 2 and 3 (P0.001), groups 2 and 1 (P0.001), but not between groups 3 and 1 (P=0.87).Based on our preliminary results, ADC values do not provide a reliable differentiation between TIN and testicular carcinoma or normal testicular parenchyma.

Intraoperative penile erection during endoscopic surgery, although an infrequent occurrence, is a troublesome complication and a challenge to the urologist. It is difficult to perform the procedure during penile erection, because various complications may occur. The etiology is unclear, and a number of pharmacological remedies have been discussed in the literature. Herein, we describe the treatment and outcomes for 3 patients with intraoperative penile erection and provide a brief review of the associated literature. Intraoperative penile erection is a rare event during transurethral procedures, with a frequency of approximately 0.1% in our institution. To our knowledge, no generally accepted protocols for the prevention or treatment of this phenomenon have been reported in the literature. We recommend intracorporeal injection of 250 microg of phenylephrine: detumescence occurred rapidly in all patients after a single injection. The mode of administration is simple, and no complications have been reported.

Induction of meiotic and post-meiotic alterations of male germ cells in vitro has been the target of several research efforts since 1960. However, to date, the establishment of an ideal culture system in which spermatogonial stem cells can be maintained and directed to proliferate and undergo meiosis and complete spermiogenesis does not exist. This is attributed to the difficulties concerning the isolation and purification of defined subpopulations of germ cells and the establishment of male germ cell lines. In addition, there is no adequate knowledge regarding the optimal biochemical conditions that promote the survival and differentiation of germ cells in long-term cultures. This review focuses on the methodologies that have been proved sufficient to achieve differentiation of cultured male germ cells. Furthermore, the factors regulating spermatogenesis and the technical prerequisites to achieve differentiation of cultured male germ cells are described. Finally, the role of in vitro cultures of immature diploid germ cells in the therapeutic management of men negative for haploid cells in their testes and the subsequent potential genetic and epigenetic risks are discussed. Hum Reprod Update

We evaluated the reproductive potential of frozen/thawed testicular spermatozoa of azoospermic men with left varicocele. The role of testicular tissue telomerase assay (TTA) in the prediction of the presence of testicular spermatozoa pre- and post-varicocelectomy was investigated, as well. Therapeutic testicular biopsy and TTA were performed in 82 nonobstructed azoospermic (NOA) men with varicoceles. Testicular spermatozoa were found in 33 men and processed for cryopreservation. Oocytes were later recovered from the spouses of the latter azoospermic men with varicoceles and injected with frozen/thawed testicular spermatozoa. Among the 49 men who were negative for testicular spermatozoa, 22 men underwent subsequently subinguinal microsurgical varicocelectomy. A total of 198 mature oocytes were successfully injected and 101 were normally fertilized and subsequently cleaved. Transfer of these 101 embryos in 26 women resulted in nine full-term pregnancies. Thirteen healthy babies were delivered. A cut-off value of TTA of 39 TPG U microg(-1) protein had an overall diagnostic accuracy equal to 90.2% to predict the presence of testicular spermatozoa pre-varicocelectomy. Within the group of men who were negative for testicular spermatozoa a cut-off value of TTA equal to 28 TPG U microg(-1) protein (pre-varicocelectomy) had a 84.2 % diagnostic accuracy to recognize the men who would become positive for either ejaculated or testicular spermatozoa post-varicocelectomy. Testicular spermatozoa can be found in 40% of NOA men with left varicocele. Ooplasmic injections with frozen/thawed testicular spermatozoa have a role in the therapeutic management of non-obstructive azoospermia associated with varicocele. Pre-varicocelectomy, a TTA cut-off value equal to 39 TPG U microg(-1) protein has a 90.2% diagnostic accuracy to indicate the men positive/negative for testicular spermatozoa. In addition, pre-varicocelectomy, a cut-off value equal to 28 TPG U microg(-1) protein has a 84.2% diagnostic accuracy to identify those men with varicoceles without testicular spermatozoa, who will become positive/negative for spermatozoa (either ejaculated or testicular) post-varicocelectomy. Andrologia

We evaluated the effects of paternal smoking on testicular function, sperm fertilizing capacity, embryonic development, and blastocyst capacity for implantation. Rats of group A were exposed to cigarette smoke for 10 weeks. Rats of group B were exposed to the smoke of incense sticks for 10 weeks. Rats of group C served as a control group. Rats of group D were exposed to cigarette smoke for 7 weeks only. Experimental period was 10 weeks in all groups. At the end of the experimental period serum testosterone responses to human chorionic gonadotropin stimulation, androgen-binding protein activity in testicular cytosols, epididymal sperm motility, and oocyte fertilization rate, oocyte cleavage rate, and blastocyst development rate after in vitro fertilization (IVF) trials were significantly smaller in group A compared with groups B and C. In contrast, fertilization rate, cleavage rate, and blastocyst development rate after intracytoplasmic sperm injection (ICSI) procedures were not significantly different among groups A, B, C, and D. Both after IVF trials and ICSI techniques, the proportion of the alive offspring to the number of transferred oocytes was significantly smaller in group A than in groups B and C. Cigarette smoke-exposure results in a secretory deficiency of Leydig and Sertoli cells leading to an impaired epididymal sperm maturation process and diminished capacity of spermatozoa to penetrate oocytes. In addition paternal cigarette smoke exposure affects the embryonic ability for implantation. Andrologia

We analyzed the effects of IL-13, IFN-γ, and IL-1βon cell viability and death of LNCaP and PC-3 cells and major signaling pathways involved in these effects. Significant increase of LNCaP cell death (apoptotic and necrotic) and increased levels of active caspase 3 were observed in cells treated with inhibitors of ERK 1/2 (UO126) and p38 (SB203580) prior to IL-1βtreatment in comparison to cells treated with UO126, SB203580, or IL-1βalone. Significant increase of LNCaP but not PC-3 cell death was detected after treatment with LY-294002 (inhibitor of phosphatidylinositol 3-kinase). No significant increase of LNCaP and PC-3 cell death was observed after treatment with SP600125 (inhibitor of JNK), SB203580 (inhibitor of p38), UO126 (inhibitor of ERK 1/2), or BAY 11-7082 (inhibitor of NF-κB). Reduced c-FLIPLexpression was observed in LNCaP cells treated with LY-294002. The significant potentiation of LNCaP cell death by inhibition of ERK 1/2, p38, and PI3-K pathways may provide a rationale for therapeutic approach in androgen-dependent prostate cancer.

We herein present a case of formation of a large infectious bladder calculous resulted from placement of a double pigtail catheter for an extensive period. The concomitant poor function of the corresponding renal unit made selection of nephroureterectomy unavoidable in the management of our patient.

Ureteric fibroepithelial polyp is a rare disease; it is of mesodermal origin and exhibits benign characteristics. Hydronephrosis occurs in rare cases, and it is generally accepted that it may result in an obstruction without causing alterations of renal function. In many cases it is difficult to differentiate from transitional cell carcinomas. Nowadays, endoscopic evaluation is the means of treatment and management. In our case study we report a patient with a long fibroepithelial polyp of the distal ureter prolapsing into the bladder in a periodic pattern. Cystoscopy revealed that movement of the polyp was moving forward and backward in the right ureteric orifice. Cold-cut biopsy established the diagnosis. The patient underwent ureteroscopic excision and remains asymptomatic a year later.

The cyclic nucleotide phosphodiesterases (PDEs) play the predominant role in the degradation of the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). The PDEs function in conjunction with adenylate cyclase (AC) and guanylate cyclase (GC) to regulate the amplitude and duration of intracellular signaling mechanisms (mediated via cAMP and cGMP, respectively). Detailed sequence analyses suggest that there are at least 11 different families of mammalian PDEs. Most of the PDEs families include more than one gene product (Bender & Beavo, 2006). In addition, many of these genes can be alternatively spliced in a tissue specific manner. The overall result is the production of different mRNAs and proteins with altered regulatory properties or subcellular localization. This multiplicity of PDE proteins allows organand cell typespecific expression and even a specific intracellular localization of PDEs in the vicinity of various protein effectors inducing fine-tuning of compartmentalized regulation for cAMP and cGMP (Zaccolo & Pozzan, 2002; Bender & Beavo, 2006). For example, cGMPhydrolyzing PDE5 is highly expressed in smooth muscle cells of the corpus cavernosum penis and vascular smooth muscle cells of the lung allowing the employment of PDE5 inhibitors for the pharmaceutical management of erectile dysfunction (Lue, 2000) and pulmonary hypertension (Ghofrani et al., 2002; Ghofrani et al., 2002; Ghofrani et al., 2003; Schermuly et al., 2004; Galie et al., 2005), respectively.

Objective: To describe the pattern of bladder cancer mortality in the Epirus district population (North-Western Greece) and to establish some relationships with cigarette smoking. Patients and methods: Mortality rates of bladder cancer in the Epirus district population were analysed according to the official data from the Department of Statistics of the University Hospital of Ioannina during the last decade (January 1990–January 2000). Age –standardization of death rates was done by the direct method, using the world population as a standard. Fisher's test was used as a significance test for linear regression coefficient in time trend analysis of mortality. Results: The average annual standardized mortality rates from bladder cancer during the study period were 5.23 per 100,000population (96% Confidence Interval – CI 4.02–5.63)in males and 1.63 per 100,000 population (96% Confidence Interval– CI 1.18–1.96) in females. Significantly increasing trends of the rates were observed in males (y = 2.421 + 0.231x; p 0.05). The greatest increase in age –specific rates in males was observed in the age group of 70 and more years (y = 25.602 + 3.673x; p < 0.01). In females,all age – specific rates except for the group 60–69 years showed significantly increasing tendency. The increasing tendency of bladder cancer mortality is followed by the rise of per capita cigarette consumption among the Epirus district population. Conclusion:Further studies are needed for the explanation of the irregularities in the age-specific rates.

Introduction: Gynecomastia is a common clinical sign in several diseases. In this report we present a case of gynecomastia with underlying testicular tumor which remained misdiagnosed for a prolonged period of time. Case Report: A 16-year-old adolescent noticed unilateral painless swelling of the left breast. He was referred to the Department of General Surgery and examined by a breast surgeon. A diagnosis of mastitis was made and a treatment with an oral antibiotic drug began. After failure of the initial antibiotic treatment, the patient was referred to the Department of Endocrinology and left testicular cancer was diagnosed. Unilateral high inguinal orchidectomy and subsequent chemotherapeutic treatment were performed. Conclusion: Primary care physicians should be aware of the possibility of a concomitant presence of gynecomastia and testicular cancer. We suggest a physical examination as well as a laboratory investigation, and testicular ultrasonography of the testes in all patients with gynecomastia.

Normal testicular function is dependent upon hormones acting through endocrine and paracrine pathways both in vivo and in vitro. Sertoli cells provide factors necessary for the successful progression of spermatogonia into spermatozoa. Sertoli cells have receptors for follicle stimulating hormone (FSH) and testosterone which are the main hormonal regulators of spermatogenesis. Hormones such as testosterone, FSH and luteinizing hormone (LH) are known to influence the germ cell fate. Their removal induces germ cell apoptosis. Proteins of the Bcl-2 family provide one signaling pathway which appears to be essential for male germ cell homeostasis. In addition to paracrine signals, germ cells also depend upon signals derived from Sertoli by direct membrane contact. Somatostatin is a regulatory peptide playing a role in the regulation of the proliferation of the male gametes. Activin A, follistatin and FSH play a role in germ cell maturation during the period when gonocytes resume mitosis to form the spermatogonial stem cells and differentiating germ cell populations. In vitro cultures systems have provided evidence that spermatogonia in advance stage of differentiation have specific regulatory mechanisms that control their fate. This review article provides an overview of the literature concerning the hormonal pathways regulating spermatogenesis. J Steroid Biochem Mol Biol

The aim of this review study is to elucidate the effects that phosphodiesterase 5 (PDE5) inhibitors exert on spermatozoa motility, capacitation process and on their ability to fertilize the oocyte. Second messenger systems such as the cAMP/adenylate cyclase (AC) system and the cGMP/guanylate cyclase (GC) system appear to regulate sperm functions. Increased levels of intracytosolic cAMP result in an enhancement of sperm motility and viability. The stimulation of GC by low doses of nitric oxide (NO) leads to an improvement or maintenance of sperm motility, whereas higher concentrations have an adverse effect on sperm parameters. Several in vivo and in vitro studies have been carried out in order to examine whether PDE5 inhibitors affect positively or negatively sperm parameters and sperm fertilizing capacity. The results of these studies are controversial. Some of these studies demonstrate no significant effects of PDE5 inhibitors on the motility, viability, and morphology of spermatozoa collected from men that have been treated with PDE5 inhibitors. On the other hand, several studies demonstrate a positive effect of PDE5 inhibitors on sperm motility both in vivo and in vitro. In vitro studies of sildenafil citrate demonstrate a stimulatory effect on sperm motility with an increase in intracellular cAMP suggesting an inhibitory action of sildenafil citrate on a PDE isoform other than the PDE5. On the other hand, tadalafil's actions appear to be associated with the inhibitory effect of this compound on PDE11. In vivo studies in men treated with vardenafil in a daily basis demonstrated a significantly larger total number of spermatozoa per ejaculate, quantitative sperm motility, and qualitative sperm motility; it has been suggested that vardenafil administration enhances the secretory function of the prostate and subsequently increases the qualitative and quantitative motility of spermatozoa. The effect that PDE5 inhibitors exert on sperm parameters may lead to the improvement of the outcome of assisted reproductive technology (ART) programs. In the future PDE5 inhibitors might serve as adjunct therapeutical agents for the alleviation of male infertility.

Pregnancies achieved by assisted reproduction technologies and particularly by ooplasmic injections of either in vivo or in vitro generated immature male germ cells are susceptible to genetic risks inherent to the male population treated with assisted reproduction and additional risks inherent to these innovative procedures. The documented, as well as the theoretical risks, are discussed in this review. These risks represent mainly the consequences of genetic abnormalities underlying male infertility and may become stimulators for the development of novel approaches and applications in the treatment of infertility. Recent data suggest that techniques employed for in vitro spermatogenesis, male somatic cell haploidization, stem cell differentiation in vitro and assisted reproductive technology may also affect the epigenetic characteristics of the male gamete, the female gamete, or may have an impact on early embryogenesis. They may be also associated with an increased risk for genomic imprinting abnormalities. Production of haploid male gametes in vitro may not allow the male gamete to undergo all the genetic and epigenetic alterations that the male gamete normally undergoes during in vivo spermatogenesis. Andrologia

Throughout the past six decades, our understanding of cancer of the prostate and the treatment of the disease using endocrine therapy has been centred on the classical investigations of Charles Huggins, which established that tumor tissue of the prostate as well as the normal tissue of the gland retained some degree of androgen dependence. Attention must now be focussed on the 20-40% of patients who are resistant to endocrine therapy. These patients are non-responders to conventional endocrine treatment after 3 to 6 months, quickly progress and die of the disease. In terms of molecular endocrinology related to the progressive stage of the disease, it would be expected that the cancer is being driven by the uncontrolled action of growth factors. Experiments combining oligonucleotide treatment with cytotoxic chemotherapeutic agents demonstrated a marked increase in the sensitivity of the prostate cancer cells. Results indicate that despite the presence of Bcl-x pre-mRNA in a number of cell types, the effects of modification of its splicing by antisense oligonucleotides vary depending on the expression profile of the treated cells. The transition from androgen-dependent to androgen non-dependent prostate cancer is accompanied by a number of molecular genetic changes, including overexpression of the Bcl-2 gene. Overexpression of Bcl-2 protein decreases the pro-apoptotic response to such cellular insults as irradiation, chemotherapy, and androgen withdrawal. The future looks promising and this kind of treatment offers a novel approach to alternative therapeutic options for advanced prostate cancer. Although numerous chemotherapeutic regimens have been evaluated for patients with hormone-refractory prostate cancer, none has improved survival.

In the present review the role of lymph node dissection in association to the prognosis of renal cell carcinoma is discussed in some details. The distribution of lymph node metastases, the extend of the lymph node dissection as well as the relation between histologic type and the incidence of nodal metastases are the points that must be well investigated. Nowdays, it seems that the complete lymph node dissection does not demonstrate any survival benefit over the radical nephrectomy alone.

Prostate cancer is the second leading malignancy in men associated with an enormous research interest in all aspects of the disease. It is well recognized that the regulation of prostatic growth is a complicated biological process. Further more the androgenic dependence of the advanced prostate cancer is well know and in the last 50 years significant progresses regarding the principle of deprivation of androgens for the treatment of the disease occured. Prostate cancer is now diagnosed in earlier stages and treatment results in increased potential for cure or extension of overall survival. Unfortunately, every treatment for prostate cancer has adverse effects with negative impact in health-related quality of life. Surgical or pharmacological castration has a significant negative impact on quality of life in patients with prostate cancer (loss of sexuality, osteoporosis, and loss of muscle mass, e.g.). Antiandrogen monotherapy is considered to be a treatment in well-informed patients who wish to remain sexually active, can be administered orally, and is well tolerated by patients with prostate cancer. This review is focused on antiandrogen monotherapy in the treatment of advanced prostate cancer.

N-acetyltransferase-2 (NAT-2) and Glutathione-S-transferase M1 and T1 (GSTM1 and GSTT1) polymorphism have been implicated in the detoxification of urothelial carcinogens, such as arylamines and polycyclic aromatic hydrocarbons. The results of epidemiological studies examining the role of NAT-2, GSTM1 and GSTT1 genotypes on the risk factors for bladder cancer were controversial, although suggesting that there may be an increased risk of the disease associated with these genotypes. The aim of the present study was to examine the independent effect and a possible interaction of NAT-2, GSTM1 and GSTT1 genotypes on the risk of bladder carcinogenesis, in the frame of a case-control study. We also investigated the possible association of specific genotype combinations with more aggressive disease in terms of tumor grading and local staging at the time of initial diagnosis. Between August 1996 and May 1998, 89 newly-diagnosed bladder cancer patients (transitional cell type) and 147 controls were included in the study. All patients were selected at the time of first diagnosis, done in the Department of Urology at the University Hospital of Ioannina, in north-western Greece. GSTM1 and NAT-2 deficient genotypes were found to be independently associated with the risk of bladder cancer (odds ratios 2.87 and 2.64, respectively). The GSTT1 genotype did not present any significant association with bladder cancer risk. We did not find a significant interaction between genotypes. These results could be explained by the independent activity of the two enzymes. Studies that will simultaneously examine the role of several genetic and environmental factors involved in bladder carcinogenesis are needed to give a global picture for the risk factors of bladder cancer and their potential interaction.

In the present review article, the penetration of antimicrobial agents into prostatic fluid and tissue was examined. Three major factors determining the diffusion and concentration of antimicrobial agents in prostatic fluid and tissue are the lipid solubility, dissociation constant (pKa) and protein binding. The normal pH of human prostatic fluid is 6.5–6.7, and it increases in chronic prostatitis, ranging from 7.0 to 8.3. A greater concentration of antimicrobial agents in the prostatic fluid occurs in the presence of a pH gradient across the membrane separating plasma from prostatic fluid. Of the available antimicrobial agents, β-lactam drugs have a low pKa and poor lipid solubility, and thus penetrate poorly into prostatic fluid, expect for some cephalosporins, which achieve greater than or equal to the inhibitory concentration. Good to excellent penetration into prostatic fluid and tissue has been demonstrated with many antimicrobial agents, including tobramycin, netilmicin, tetracyclines, macrolides, quinolones, sulfonamides and nitrofurantoin.

A rare case of orbital metastasis from carcinoma of the prostate in a 76-year-old man who presented with pain in his left eye, mild proptosis and reduced visual acuity is reported. Cranial CT scanning demonstrated large bone metastases in the left orbit. The patient underwent orbital evisceration. The histopathological studies that were based on the morphological and immunohistochemical findings confirmed the histological diagnosis of orbital metastasis arising from prostatic carcinoma with neuroendocrine features.

Numerous modalities of treatment have been used in the past to control massive bladder haematuria, with varying degrees of success. Formalin has been used in urology only for the treatment of intractable haematuria of inoperable bladder carcinomas, usually as the last resort when all other nonsurgical attempts have failed and before more aggressive surgical measures are considered. Eight patients with bladder tumours classified T2 (2 cases), T3 (2 cases) or T4 (4 cases) and 2 patients with radiation cystitis were assessed as being beyond the scope of even palliative surgery, severe haemorrhage being present in all cases. The treatment was instituted in all cases by intravesical instillation of a 10 per cent formalin solution under general anaesthesia. Four patients received 4 and 6 instillations, respectively, the former over 4 weeks and the latter over 10 months. The bladder was filled completely and an indwelling-catheter introduced, the formalin solution being left in the bladder for 5 to 30 min (mean: 12 min). Haematuria was absent after 1 to 25 days (mean: 11 days) in 9 cases. The 10th patient died before arrest of haemorrhage. Survival after instillation was 65 days to 27 months (mean: 11.5 months). The outcome was fatal within 4 months or less in 3 cases and 4 patients died of renal failure within 3 months, one within 65 days after instillation. In 4 cases, treatment with formalin reduced bladder capacity to less than 100 ml. Other complications included retroperitoneal fibrosis (1 case), urinary incontinence (3 cases) and severe frequency and nocturia (3 cases). This procedure should therefore be reserved for terminal cases unable to support more aggressive therapy. Int Urol Nephrol

Introduction Penile cancer is uncommon. When penile cancer is left untreated, at an advanced stage it can have tragic consequences for the patient. Case presentation Our case report does not concern a new manifestation of penile cancer, but an interesting presentation with clinical significance that emphasizes the need to diagnose and treat penile cancer early. It is an unusual case of a neglected penile cancer in a 57-year-old Greek man that led to auto-amputation of the penis and a large chasm in the lower abdominal wall. The clinical staging was T4N3M0 and our patient was treated with a bilateral cutaneous ureterostomy, chemotherapy and radiotherapy. Our patient died 18 months after his first admission in our clinic. Conclusions Emphasis must be placed on early diagnosis and treatment of penile cancer, so further development of the disease can be prevented.