SPTBN1 Mediates the Cytoplasmic Constraint of PTTG1, Impairing Its Oncogenic Activity in Human Seminoma.

Seminoma is the most common testicular cancer. Pituitary tumor-transforming gene 1 (PTTG1) is a securin showing oncogenic activity in several tumors. We previously demonstrated that nuclear PTTG1 promotes seminoma tumor invasion through its transcriptional activity on matrix metalloproteinase 2 (MMP-2) and E-cadherin (CDH1). We wondered if specific interactors could affect its subcellular distribution. To this aim, we investigated the PTTG1 interactome in seminoma cell lines showing different PTTG1 nuclear levels correlated with invasive properties. A proteomic approach upon PTTG1 immunoprecipitation uncovered new specific securin interactors. Western blot, confocal microscopy, cytoplasmic/nuclear fractionation, sphere-forming assay, and Atlas database interrogation were performed to validate the proteomic results and to investigate the interplay between PTTG1 and newly uncovered partners. We observed that spectrin beta-chain (SPTBN1) and PTTG1 were cofactors, with SPTBN1 anchoring the securin in the cytoplasm. SPTBN1 downregulation determined PTTG1 nuclear translocation, promoting its invasive capability. Moreover, a PTTG1 deletion mutant lacking SPTBN1 binding was strongly localized in the nucleus. The Atlas database revealed that seminomas that contained higher nuclear PTTG1 levels showed significantly lower SPTBN1 levels in comparison to non-seminomas. In human seminoma specimens, we found a strong PTTG1/SPTBN1 colocalization that decreases in areas with nuclear PTTG1 distribution. Overall, these results suggest that SPTBN1, along with PTTG1, is a potential prognostic factor useful in the clinical management of seminoma.

Male sexual dysfunction in patients with chronic end-stage renal insufficiency and in renal transplant recipients.

MATERIALS AND METHODS: The study was conducted from December 2011 to December 2012 on 95 patients between the ages of 20 and 65 years: 44 of which had been undergoing dialysis for over a year and 51 of whom had undergone kidney transplants more than 6 months before. Comorbidities were carefully recorded, erectile function was evaluated the with IIEF5 questionnaire and serum levels of total testosterone / free and prolactin were tested at early morning (7 AM). To assess the relationship between erectile dysfunction (ED) and clinical laboratory tests, Student's t-test statistical (quantitative variables), chi-square (qualitative variables), the uni and multivariate analysis were used. RESULTS: In patients undergoing dialysis and in recently transplanted patients a higher instance of ED was found (70% and 65% of cases respectively). Amongst dialyzed patients, patients aged over 50 suffer from ED more frequently. Patients aged over 50s represent 61% of the total number of patients suffering from ED, and just 31% of patients not suffering from ED, (p = 0.006); Hyperprolactinemia was found in 23% and 20% of both groups respectively. Fifty nine % of the dialyzed patients presented values of testosterone serum levels of less than 250 ng/dl with a significant difference between those who were suffering from ED and those who were not (65% of ED patients vs. 46%,of patients not affected from ED p = 0.019). This was found in only 37% of transplanted patients and there does not appear to be a statistically significant correlation with the onset of ED (p = 0.12). In patients over the age of 50, diabetes and a condition of hypotestosteronemia were significantly correlated with ED at univariate and multivariate analyses. CONCLUSIONS: The ED in patients with end stage chronic kidney failure (CKF) continues to have a strong prevalence, either in the patients who are undergoing dialysis or in those who have received transplants. In literature this issue is not sufficiently considered if not at all. Hypotestosteronemia is a risk factor for the onset of ED in end stage CKF patients. A significantly lower prevalence of hypogonadism among dialyzed patents and transplant recipients suggests that renal transplantation may be protective for the sexual capabilities of these patients.

Sexual outcomes after organ potency-sparing surgery and glans reconstruction in patients with penile carcinoma.

INTRODUCTION: Radical surgery is the "gold standard" for treatment of invasive penile carcinoma but very poor aesthetic, functional and psychological outcomes have been reported. Our purpose was to assess the impact of organ potency-sparing surgery in locally confined carcinoma of the penis. MATERIALS AND METHODS: We evaluated retrospectively 42 patients with early penile cancer (Ta,T1,T2), treated with glandulectomy and glanduloplasty with urethral mucosa and sparing of cavernosal apexes, or glandulectomy and limited apical resection in cases of Stage T2. Sexual function, ejaculation and libido were evaluated with an IIEF-15 questionnaire before the appearance of neoplasia (about three months before the surgery) and six months after surgery. Quality of life was evaluated by the Bigelow-Young questionnaire. The scores relating to two weeks prior to the surgery have been compared to those obtained six months after surgery. The statistical analysis was conducted using t-Student for repeated measures and analysis of variance. RESULTS: Six months after surgery 73% of patients reported spontaneous rigid erections, 60% coital activity while 76% of the group treated with urethral glanduloplasty reported normal ejaculation and orgasm, regained an average of 35 days after surgery. The average IIEF-15 scores reported in the entire series in the domains of erection, libido and coital activity of the pre-cancer period were not statistically different than those recorded six months after surgery. In the group treated with glandular reconstruction, pre-and postoperative IIEF-15 mean scores related to ejaculation and orgasm domains were not significantly different. Mean scores of Bigelow-Young questionnaires related to sexual pleasure, familial, social and professional relationships showed significant improvement after surgery. CONCLUSIONS: Potency sparing-sparing surgical treatments have a positive impact on a wide spectrum of the patient's life including family relationships, and social and working conditions.

Simultaneous surgical management of renal cancer with atrial thrombotic extension and severe chronic coronary artery disease: a case report.

BACKGROUND: Renal cell carcinoma accounts for 2-3% of all malignant cancers in adults and is characterized by the potential development of venous tumor thrombus. CASE PRESENTATION: We present a rare case of a 62-year-old Caucasian man who arrived in the emergency department for monosymptomatic hematuria. Further investigation revealed a right renal cell carcinoma with 16 cm intravascular extension through the renal vein into the inferior vena cava and right atrium associated with significant coronary artery disease based on the computed tomography scan and coronary angiography. To the best of our knowledge, after an extensive literature review, only one similar case has been reported with involvement of the contralateral kidney. Therefore, there are no applicable management recommendations. After performing coronary artery bypass graft surgery, we proceeded with an open right radical nephrectomy and inferior vena cava and right atrium thrombectomy under cardiopulmonary bypass and while the patient's heart was still beating. The postoperative course went without complications, and the patient was discharged from the hospital on the 10th postoperative day. CONCLUSIONS: Radical nephrectomy and thrombectomy with reconstruction of the inferior vena cava combined with coronary artery bypass graft can be performed safely and effectively in selected patients with renal cell carcinoma and significant coronary artery disease. Multidisciplinary teamwork and careful patient selection are essential for optimal outcomes.

Efficacy of an assisted low-intensity programme of perioperative pelvic floor muscle training in improving the recovery of continence after radical prostatectomy: a randomized controlled trial.

UNLABELLED: Study Type - Therapy (RCT) Level of Evidence 1b. What's known on the subject? and What does the study add? Peri-operative pelvic floor muscle training reduces urinary incontinence for men undergoing radical prostatectomy (RP). A preoperative biofeedback session, combined with postoperative pelvic floor muscle training, and assisted sessions on a monthly basis only, is an effective low-intensity programme to improve recovery of continence in patients undergoing RP. OBJECTIVE: To evaluate the efficacy of preoperative biofeedback (BFB) combined with an assisted low-intensity programme of postoperative perineal physiokinesitherapy in reducing the incidence, duration and severity of urinary incontinence (UI) in patients undergoing radical prostatectomy (RP). PATIENTS AND METHODS: A prospective, single-centre, randomized controlled clinical study was designed. • The intervention group received a training session with BFB, supervised oral and written instructions on Kegel exercises and a structured programme of postoperative exercises on the day before open RP. After RP, patients received control visits, including a session of BFB, at monthly intervals only. • The control group received, after catheter removal, only oral and written instructions on Kegel exercises to be performed at home. Patients received control visits at 1, 3 and 6 months after catheter removal. • At each visit the number of incontinence episodes, the number of pads used and patient-reported outcome measures (International Consultation on Incontinence Questionnaire on Urinary Incontinence [ICIQ-UI], [ICIQ]-Overactive Bladder [OAB], University of California, Los Angeles-Prostate Cancer Index [UCLA-PCI], International Prostate Symptom Score-Quality of Life [IPSS-QoL]) were assessed in both groups. All patients were followed-up for a period of at least 6 months after catheter removal. • The primary outcome was the recovery of continence, strictly defined as a ICIQ-UI score of zero. RESULTS: Overall, 34 consecutive patients were eligible and 32 were available for the final analysis: 16 patients for each study group. The two groups were homogeneous for all pre- and intraoperative features examined. • In the intervention group, continence had been achieved by six, eight and 10 patients at 1-, 3- and 6-month follow-ups, respectively, vs no patients (P= 0.02), one patient (P= 0.01) and one patient (P= 0.002) in the control group at each follow-up, respectively. • The analysis of the UCLA-PCI and ICIQ-OAB scores, the number of incontinence episodes per week and the number of pads per week showed significant differences in favour of patients in the intervention group at 3 and 6 months. • Patients in the intervention group reported better IPSS-QoL scores at all follow-up times but the difference did not reach statistical significance. CONCLUSIONS: Preoperative BFB combined with a postoperative programme of perineal physiokinesitherapy and assisted sessions on a monthly basis only, is a treatment strategy significantly more effective than the standard care in improving recovery of continence in patients undergoing RP. • The impact on QoL appeared less evident, although a trend for a better QoL was observed in the intervention group.

Urological complications following inguinal hernioplasty.

Aim of this paper is to report a systematic review of the literature about the incidence and putative mechanisms of genital tract injuries following open and laparoscopic herniorraphy and their effects on sexual function and fertility and to point out the measures of prevention and of treatment. The most frequently described events have been intraoperative complications as bladder or spermatic cord structure damage, immediate postoperative complications as ischaemic orchitis, urinary retention, urinary tract infection, hydrocele or scrotal haematoma and bacterial orchitis, or long-term complications as chronic orchialgia, testis atrophy, sexual dysfunction and infertility. The evidence of literature shows that urological complication after hernioplasty are under-reported. Only a small number of studies to date have essentially dealt with sexual quality of life after inguinal hernia surgical repair. The sexual needs of patients with groin hernias are rarely discussed. Extensive laparoscopic procedures, due to the need of learning curve, have increased the risk of vas damage and infertility in young patients candidate to hernioplasty. Early diagnosis prevents urological complication as well as possible legal claims after hernia repair: it should be include careful history, objective and subjective symptoms and signs of uro-genital pathologies, lab data when necessary, immediate eco-color-Doppler imaging and urgent urological consultation. Despite the lack of prospective randomized trials, there is a growing evidence in literature about positive impact of hernioplasty on sexual function, encouraging future studies on this issue.

PTTG1/ZEB1 Axis Regulates E-Cadherin Expression in Human Seminoma.

(1) Background: PTTG1 sustains the EMT process and the invasiveness of several neoplasms. We previously showed the role of nuclear PTTG1 in promoting invasiveness, through its transcriptional target MMP2, in seminoma in vitro models. Here, we investigated the key players involved in PTTG1-mediated EMT in human seminoma. (2) Methods: Two seminoma cell lines and four human seminoma tumor specimens were used. E-Cadherin gene regulation was investigated using Western blot, real-time PCR, and luciferase assay. Immunoprecipitation, ChIP, RE-ChIP, and confocal microscopy analysis were performed to evaluate the interplay between PTTG1 and ZEB1. Matrigel invasion and spheroid formation assays were applied to functionally investigate PTTG1 involvement in the EMT of seminoma cell lines. RNA depletion and overexpression experiments were performed to verify the role of PTTG1/ZEB1 in E-Cadherin repression and seminoma invasiveness. E-Cadherin and ZEB1 levels were analyzed in human testicular tumors from the Atlas database. (3) Results: PTTG1 transcriptionally represses E-Cadherin in seminoma cell lines through ZEB1. The cooperation of PTTG1 with ZEB1 has a significant impact on cell growth/invasion properties involving the EMT process. Analysis of the Atlas database of testicular tumors showed significantly lower E-Cadherin levels in seminoma, where PTTG1 showed nuclear staining. Finally, PTTG1 and ZEB1 strongly localize together in the periphery of the tumors. (4) Conclusions: These results strengthen the evidence for a role of PTTG1 in the EMT process in human seminomas through its cooperation with the transcriptional repressor ZEB1 on the E-Cadherin gene. Our data enrich the molecular characterization of seminoma, suggesting that PTTG1 is a prognostic factor in seminoma clinical management.

Imaging of renal cell carcinoma: state of the art and recent advances.

BACKGROUND AND AIM: Renal cell carcinoma (RCC) is the 13th most common cancer worldwide and accounts for 4% of all adult malignancies. Herein the state of the art and recent advances in cross-sectional radiological imaging applied to RCC are reviewed, including ultrasonography, computed tomography, magnetic resonance imaging, and positron emission tomography. METHODS: Literature search of peer-reviewed papers published by October 2010. RESULTS: In front of more conventional and widespread imaging tools, such as ultrasonography and computed tomography, an array of newer and attractive radiological modalities are under investigation and show promise to improve our ability to noninvasively detect renal tumors and its recurrences, accurately assess the extent of the disease, and reliably evaluate treatment response, particularly in the era of antiangiogenetic therapy. CONCLUSIONS: Recent major advances in radiological imaging techniques have considerably improved our ability to diagnose, stage and follow-up RCC. Further studies are needed to evaluate the potential of most recent and still investigational imaging tools.

Imaging in prostate cancer diagnosis: present role and future perspectives.

Prostate cancer (PCa) remains a major health concern for the male population. Detection and primary diagnosis of PCa are based on digital rectal examination, serum prostate-specific antigen levels, and transrectal ultrasound (TRUS)-guided random biopsy. Moreover, the gold standard for detecting PCa, systematic biopsy, lacks sensitivity as well as grading accuracy. This review summarizes recent developments of ultrasonography modalities and functional magnetic resonance imaging (MRI) in the diagnosis of PCa. A comparison between the different methods is presented, including their clinical value and usefulness. It is concluded that innovative ultrasound techniques (including ultrasound contrast agents, 3-D and 4-D sonography, elastography and harmonic sonography) promise benefits in comparison to standard TRUS to accurately diagnose PCa. Promising advances have been made in the detection of PCa with multiparametric MRI. The combination of conventional and functional MRI techniques (including diffusion-weighted imaging, dynamic contrast-enhanced MRI, and MR spectroscopy) can provide information for differentiating PCa from noncancerous tissue and can be used for MRI-guided biopsies, especially in patients with persistent elevation of serum prostate-specific antigen and previous negative TRUS-guided biopsies. However, functional MRI technique and MRI-guided biopsy remain expensive and complex tools presenting inherent challenges.

Is microsurgical technique really necessary in inguinal or sub-inguinal surgical treatment of varicocele?

The ideal method for treatment of varicocele is still controversial. The techniques of inguinal and sub-inguinal ligation, although less invasive than "high" abdominal ligations (Palomo, Ivanissevich), have been less popular than the former ones. Up to now most authors have considered as mandatory microsurgical techniques for the ligation of spermatic veins at inguinal or sub-inguinal level, or at least instruments of optical magnification in order to preserve testicular arterial supply of the spermatic and cremasteric artery at groin and to prevent testicular atrophia or gonadic ischemia. The aim of this study was to assess clinical outcomes of open surgical technique of varicocele repair compared to results derived from microsurgical series. A retrospective study included 45 patients of mean age 31 years (range 18-39) that underwent open surgical technique of inguinal ligation of spermatic veins in the period 2004-2009; clinical results of this series were compared with those obtained in five relevant studies derived from systematic review of the literature on microsurgical techniques. The pre-operatory evaluation in our series included a physical examination, a minimum of two semen analysis and scrotal color Doppler ultrasound. Post-operative pain, complication rates, days of hospitalization and time to return to work were considered as main outcomes. All patients were evaluated at 1 week, at 3 and 6 months after the operation by means of a physical examination, scrotal Doppler ultrasound and sperm analysis. Most patients (39/45) presented no pain in the first week, 6/45 mild to moderate pain (mean VAS score 2). None of the patients reported pain in the weeks thereafter The hospitalization (1.8 +/- 0.7 days) and the time for return to work (7.2 +/- 3.2 days) were not significantly different in microsurgical and open groups. During follow-up no complications like hydrocele or testicular atrophy were observed. Doppler ultrasound carried out 3 and 6 months after surgery, pointed out no reflux in testicular veins in 41/45 cases while in 4/45 it showed a persistence of reflux grade I, less than the grade before the treatment. Comparing pre-and post-operatory sperm analysis allowed us to observe a significant improvement either in spermatozoa concentration (22 +/- 4 40_+/- 6 millions/ml, p < 0.01), either in motility (33 +/- 4% and 48 +/- 4%, p < 0.05), without significant changes in morphology. No significant differences were recorded comparing these data with those coming from microsurgical series. Our study reported positive clinical outcomes using the technique of sub-inguinal surgical ligature of varicocele without using microsurgical techniques or instruments of optical magnification. The operative time, complication and relapse rates, Doppler flow parameters and semen parameters were not significantly different from those reported in the literature of microsurgical techniques, with the advantage of such a simple surgical technique combined with cost savings and patient's comfort.

Paraneoplastic syndromes in patients with urological malignancies.

INTRODUCTION: Paraneoplastic syndromes (PNS) may represent the main clinical problem in cancer patients; however, the knowledge of their clinical aspect remains quite poor among urologists. OBJECTIVE: To provide urologists with an overview on main clinical aspects of PNS that have been reported to be associated to urological cancers. METHODS: Literature search of peer-reviewed papers published by July 2008. RESULTS: All genitourinary tumors can cause a PNS, and renal cell carcinoma is the most frequent urological malignancy involved. Prostate cancer is the second urological tumor associated with PNS which, conversely, are uncommon in bladder cancer and rare in testicular cancer. Tumor neuroendocrine differentiation is involved in most endocrine PNS. Neurologic PNS are very uncommon but may dominate the clinical picture and need a high suspicion index to be recognized. Important advances have been made on radionuclide scan methods in order to detect the primary tumor. The most effective treatment strategy is always represented by the radical therapy of the underlying cancer, but specific therapeutic options are sometimes available. CONCLUSIONS: Endocrine PNS are frequently associated with urological cancers, especially renal and prostate carcinoma. PNS have been rarely reported in association with cancers of bladder, urethra and testicle.

Disseminated intravascular coagulation secondary to metastatic prostate cancer: case report and review of the literature.

Disseminated intravascular coagulation (DIC) is the most frequent coagulation disorder associated with metastatic prostate cancer. We report a case of a 60-year-old white man who was admitted in our department with ecchymoses and haematuria secondary to a DIC associated with metastatic prostate cancer. A review of this clinical scenario is also reported.

Protein Expression of PTTG-1, OCT-4, and KLF-4 in Seminoma: A Pilot Study.

Seminomas are the most frequent kind of testicular germ cell tumors (TGCTs), accounting for 50% of tumor diagnosis in young men, whereas non-seminomas account for 40% and mixed forms for 10% of cases. It is currently supposed that TGCTs evolve from a pre-invasive stage of carcinoma in situ (CIS). Octamer-binding transcription factor 4 (OCT4) is essential for self-renewal of stem cells. It is considered as a major regulator of cell pluripotency. Prior studies have shown that seminoma expresses OCT4. Transcription factor Krüppel-like factor 4 (KLF4) has moreover associated with embryonic stem cell maintenance. Finally, we previously demonstrated the expression of PTTG1 in CIS and seminomas. In this pilot study, we compared the combined expression of PTTG1 with KLF4 and OCT4 in seminoma, in order to validate our hypotesis that PTTG1 marks a specific population of stem cells in neoplastic tissue, strictly related with tumor. Formalin-fixed and paraffin-embedded testicular tissues by 5 patients who underwent an orchidectomy for seminoma have been collected and immunofluorescence analysis was performed using antibody rabbit monoclonal PTTG-1 and mouse monoclonal OCT4 or mouse monoclonal KLF4 antibody. In seminoma we observed that tumor cells strongly express OCT-4 in all seminomas and in the intratubular areas of seminoma. Expression of KLF-4 was observed in many tumor cells. PTTG1 marks some specific OCT4- and KLF4-positive tumor cells, mainly localized at the periphery of the neoplasm. In the intertubular infiltration areas nests of cells expressing both OCT4/KLF4 and PTTG1 have been observed. This is the first identification of a cell population in seminoma characterized for being OCT4, KLF4, and PTTG1 positive cells in seminoma, associated with cancer invasiveness. Further investigation is needed to elucidate if a functional abrogation of PTTG1 might be used in order to offer new therapeutic approaches in the clinical workout of seminoma.

Germ Cell Neoplasia in situ (GCNIS) in Testis-Sparing Surgery (TSS) for Small Testicular Masses (STMs).

Purpose: The testis-sparing surgery (TSS) is surgical technique accepted for small testicular masses (STMs). Frozen section examination (FSE) is an essential assessment at the time of TSS. The aim of this study is to measure the maximum distance of the foci of ITGCN from STMs. Methods: In our hospital between June 2010 and October 2017 a total of 68 patients with STM underwent a TSS. All the testis specimens were totally embedded and processed via the whole-mount method and a diagnosis of germ cell tumor with GCNIS were made. The distance between STMs and GCNIS were calculated by two pathologists directly on the slides considering for the third dimension the number of the paraffin blocks in which the foci of GCNIS were found. Results: The STMs were classic seminoma in 62 out 68 cases, embryonal carcinoma in 4 cases, while in 2 case a diagnose of mixed germ cell tumor were made. The size of the STMs was between 0.5 and 2 cm and the foci of GCNIS were observed in seminiferous tubules very closed to SMTs or as skip lesions in the surrounding testicular parenchyma, dispersed in normal testis. In 48 out of 68 cases (70.5%) foci of GCNIS were at the distance from SMTS of 1.5 cm or below and in 60 out of 68 cases (88%) at the distance of 2 cm or below The distance of GCNIS from the STMs was not related to the histological subtype of the germ cell tumor, while there is a linear correlation between size of the STMs and the distance of foci of GCNIS (p = 0.0105; r = 0.9167). Conclusion: Our data showed that foci of ITGCN were not observed beyond 2.5 cm from the STM. In particular we demonstrated that exist a linear correlation between size of STMs and distance of the foci of GCNIS from STMs (p = 0.0105; r = 0.9167). In conclusion mapping the tissue around the tumor not randomly but in targeted areas could reduce the false negative biopsies of the testis with GCNIS, increasing the radicality of the TSS procedure.

Extracorporeal shockwave lithotripsy in pediatrics.

Since its introduction in 1980, extracorporeal shockwave lithotripsy (SWL) has become the first therapeutic option in most cases of upper-tract urolithiasis, and the technique has been used for pediatric renal stones since the first report of success in 1986. Lithotripter effectiveness depends on the power expressed at the focal point. Closely correlated with the power is the pain produced by the shockwaves. By reducing the dimensions of the focus, it becomes possible to treat the patient without anesthesia or analgesia but at the cost of a higher re-treatment rate. Older children often tolerate SWL under intravenous sedation, and minimal anesthesia is applicable for most patients treated with second- and third-generation lithotripters. Ureteral stenting before SWL has been controversial. Current data suggest that preoperative stent placement should be reserved for a few specific cases. Stone-free rates in pediatric SWL exceed 70% at 3 months, with the rate reaching 100% in many series. Even the low-birth-weight infant can be treated with a stone-free as high as 100%. How can one explain the good results? Possible explanations include the lesser length of the child's ureter, which partially compensates for the narrower lumen. Moreover, the pediatric ureter is more elastic and distensible, which facilitates passage of stone fragments and prevents impaction. Another factor is shockwave reproduction in the body: there is a 10% to 20% damping of shockwave energy as it travels through 6 cm of body tissue, so the small body volume of the child allows the shockwaves to be transmitted with little loss of energy. There are several concerns regarding the possible detrimental effect of shockwaves on growing kidneys. Various renal injures have been documented with all type of lithotripters. On the other hand, several studies have not shown adverse effects. In general, SWL is considered to be the method of choice for managing the majority of urinary stones in children of all ages. Re-treatments improve the stone-free rate, often raising it to 100%. Among the predictors of success, stone size seems to be the most important. In the absence of guidelines, selecting the appropriate treatment modality for each child requires planning and depends on instrument availability and local expertise.

The cost of treatment and follow-up of bladder cancer in Italy.

OBJECTIVES: To evaluate the costs of bladder bladder cancer treatment and follow-up. MATERIALS AND METHODS: A purely economic analysis was carried out evaluating in our Institution a) the cost of an hospital stay of patients submitted to transurethral resection of superficial bladder cancer and to radical cystectomy for invasive bladder cancer, b) the cost of endovesical immuno-chemotherapy performed as day hospital regimen, c) the cost of the first year of follow-up according to European Association of Urology's Guidelines as outpatient regimen. RESULTS: The total cost related to a superficial tumour of the bladder treated with an endoscopic resection amounts to Euro 2,242.20, while in case of invasive bladder cancer treated with a radical cystectomy it comes to Euro 6,860. For chemo-immunotherapy the costs in a day hospital regimen related to a 8-weekly session of mitomicin, 6-weekly session of epirubicin and BCG are Euro 1,420, Euro 1,037 and Euro 975, respectively. The first year of follow-up for a patient with low risk of superficial bladder cancer without recurrence costs Euro 265.15. In case of high risk superficial bladder cancer the cost reaches Euro 321.75. In case of a patient with invasive bladder cancer in the first year, when follow-up is more strict, expenses amount to Euro 548.90. CONCLUSIONS: Cancer bladder is a high-cost illness due, in particular, to its heterogeneity in presentation and high rate of recurrences which makes any evaluation underestimated. The possibility of containing costs is essentially related to optimization of the follow-up and to the development of optimal therapeutic procedures which could lead to a reduction in the number of recurrences.

High intensity focused ultrasound as first line salvage therapy in prostate cancer local relapse after radical prostatectomy: 4-year follow-up outcomes.

BACKGROUND: Prostate cancer (PCa) is the most commonly diagnosed malignancy in men and the second leading cause of cancer death in developed countries. Despite the primary treatments, 20-30% of patients experience a recurrence. The main objective of this study was to evaluate the clinical efficacy of salvage high intensity focused ultrasound (HIF U) after radical prostatectomy in terms of biochemical free survival rate (BFSR) and PSA nadir. METHODS: Twenty two patients with local recurrence of Pca after radical prostatectomy underwent HIFU as first-line salvage therapy. Considering that in all HIFU experiences, PSA nadir and PSA failure are different and PSA definition of BFSR is unknown, we defined treatment success as a PSA nadir ≤0.4 ng/mL 3 months after treatment. All early and late medical and surgical complications were recorded. RESULTS: Ten of the 22 patients (45.5%) were classified as "success" three months after HIFU, showing a nadir PSA≤0.4 ng/mL; 12/22 patients (54.5%) were classified as "failure" during follow-up (median follow-up: 48 months). Seventeen of 22 (77%) patients were continent (no-pad) before HIFU. A new diagnosis of stress urinary incontinence was made in 5 cases (early onset) after treatment. A case of vesicoureteral anastomotic stenosis was treated, endoscopically through cold urethrotomy. We did not observe cases of recto-urinary fistula or persistent lower urinary tract symptoms. Two sevenths of the patients complained about de novo erectile dysfunction after HIFU. CONCLUSIONS: The positive oncologic outcomes in the short term anyway obtained in selected patients, associated with documented mild side effects, represent the basis to start more organic, prospective, randomized and multicenter study protocols, that with a long term follow-up could confirm these promising preliminary results.

[Male infertility: non-surgical therapy]. / Infertilità maschile: terapia non chirurgica.

Infertility is defined as the inability of a couple to conceive after 12 months of unprotected intercourse and affects 15% of couples with male component of 50%. The failure of spermatogenesis can result from hypothalamic, pituitary or testicular disorders although in the majority of cases it remains idiopathic. The diagnostic process includes medical history, semen analysis, hormonal studies, genetic studies and radiological evaluation.Targeted hormonal therapies are available for patients whose infertility is caused by altered levels of androgens, prolactin, or TSH. Main treatments aim to restore normal sexual function by administering testosterone and to increase spermatogenesis with pulsatile GnRH.Fertility in men suffering from hypogonadotrophic hypogonadism can be restored through hormone therapy using GnRH or with the use of gonadotropins when there is hypothalamic failure. In the past, treatment options for the factors of idiopathic male infertility were mainly based on the use of anti-estrogens that cause an increased secretion of FSH and LH and therefore of testosterone.Oxytocin promotes the progression of the sperm and increases the conversion of testosterone into dihydrotestosterone. The aromatase's inhibitors decrease the conversion of androgens to estrogens, increasing serum levels of androgens, resulting in an increased release of gonadotropins.Two areas showed interesting future perspectives for the treatment of infertility: gene therapy and transplantation of spermatogonial stem cells.

Discovery history and clinical development of mirabegron for the treatment of overactive bladder and urinary incontinence.

INTRODUCTION: Overactive bladder (OAB) and urinary incontinence, although not life-threatening, are very bothersome chronic health conditions. The limitations of current pharmacological treatment urge the need for novel drugs with alternative mechanisms of action. Huge efforts in this area of research led to the synthesis of several selective and potent ß3-adrenoceptor agonists that gained relevance through research during the late 80s and 90s. Mirabegron was the first compound of this new class of drugs that showed preclinical efficacy in several models of storage bladder dysfunction, together with a favorable human pharmacological profile. Having passed the proof-of-concept stage, an extensive clinical development and pharmacology program was performed during the last 10 years, involving >10,000 individuals, before mirabegron was granted marketing approval. AREAS COVERED: In this case history, the authors review the milestones in mirabegron's discovery based on a systematic literature review. EXPERT OPINION: Thanks to its tolerability and safety/efficacy balance, mirabegron has potential to fill a need for new treatment options for OAB, and paves the way for further development of a completely new class of drugs aimed to treat this condition. However, the exact role of mirabegron in clinical practice has yet to be defined. Further studies are needed in order to clarify, together with post-launch information, critical safety issues and cost-effectiveness in head-to-head comparison with current standard treatments.

[Therapeutic strategies in penile cancer: state of the art]. / Strategie terapeutiche nel tumore del pene: stato dell'arte.

A systematic review of the current treatment options and of the outcomes of penile carcinoma has been performed with special focus on controversial issues. A MedLine search using specified search terms was done during the period 1988 - January 2013. Demolitive surgery is considered as the "gold standard" treatment of invasive penile carcinoma staged higher than T2, but negative psychological outcomes were reported. On the other hand, conservative surgical techniques have been associated with higher recurrence rates. Potency-sparing technique (glansectomy and apexes sparing) preserves penile length: the reconstruction of glans anatomy and function is a key point to restore anatomy and sexual functions. Techniques such as glanduloplasty have given satisfactory anatomic, functional and sexual outcomes. Lymphadenectomy is indicated in any case of inguinal palpable nodes that persist after a course of antibiotic therapy, but also in all the cases staged T2 or higher, or in any high-grade penile cancer. It is still being debated the extension of inguinal lymphadenectomy for penile cancer: unilateral, bilateral, and extended to pelvic lymph nodes. Due to the specific radioresistance of penile cancer, radiation therapy is currently indicated in case of unresectable penile cancers with palliative intent. Chemotherapy is indicated as adjuvant therapy for stage T1-T3, N1-3, M0, or as neo-adjuvant therapy in the event of extensive pelvic and inguinal lymphadenopathies, or as palliative treatment in patients with unresectable or metastatic cancers. New chemotherapy agents such as Cis - platinum and Taxanes have shown promising results in early trials.