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Objective: The objective of this study was to challenge the activity of a promising intravesical drug (gemcitabine), administered at an intensive regimen (2,000 mg twice a week for 6 weeks) in treatment naïve CIS of the bladder and to observe side-effects. The statistical design was conceived to provide sufficient information through the enrollment of a low number of patients., Material and Methods: Primary, secondary, and concurrent CIS with no prior intravesical therapy were eligible. Treatment schedule: 2000 mg gemcitabine in 50 ml saline, unbuffered, for 1 hour twice a week for 6 weeks. Complete response (CR) = negative cytology and negative cystoscopy + bladder mapping at 3 months. Failure (FA) = all other situations. Side-effects were recorded according to Common Terminology Criteria for Adverse Events (CTCAE)., Study Design: A 3-stage design. After testing the drug on 11 patients in the first stage, the trial had to be terminated if 3 or fewer CRs. After testing the drug on 21 patients in the first and second stages, the trial had to be terminated if 7 or fewer CRs. After testing the drug on 32 patients in all 3 stages, the drug was considered active in case of >12 CRs. Survival data up to 4 years from trial closure were collected., Results: The study proceeded to stage II since 5/11 responded at stage I but it was stopped after including 18 patients due to side-effects; 6/18 had primary CIS, 7 had secondary CIS, and 5 concomitant CIS; 6/18 (33.3%) had grade 3 side-effects (4 G3 cystitis, 3 G3 leucopenia), leading to stopping the treatment in all 6 cases. CRs were observed in 8/18 patients (44.4%), FA in 10/18 (55.5%). Median overall survival (OS) was 44 months with a 4-year cancer-specific survival of 100%., Conclusion: Biweekly gemcitabine as first line treatment for CIS led to excess toxicity and suboptimal activity. Due to the peculiar statistical design, a negative response was generated enrolling a low number of patients. The absolute 4-year CSS suggests that no window of opportunity for disease cure may have been lost by assessing a new, non standard, treatment for CIS., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Bladder cancer is the most common tumor of the urinary tract, with a worldwide incidence of 8.6 x 100000 in men and 2.6 x 100000 in women (1). The majority of patients (75-85%) present as non-muscle invasive bladder cancer (NMIBC); within this category the most represented stage is Ta (70%), followed by T1 (20%) and, less frequently, carcinoma in situ (CIS) (10%) (2). The diagnosis of NMIBC and, more generally, of bladder cancer, depends on urine cytology and endoscopic examination with histological evaluation of the resected tissue. Clearly, an optimal cystoscopy with accurate transurethral resection (TUR) is of great importance in order to improve the detection rate and to reduce the probability of recurrence and progression. Today the cystoscopy is routinely performed with the white light technique (WLC), the same of about 80 years ago (3). Several studies have demonstrated that an initial TUR with WLC can miss small papillary lesions and, particularly, flat lesions such as CIS. Moreover, recurrence rates of non-muscle invasive bladder cancer (NMIBC) are directly related to the possibility of achieving a complete resection: residual cancer is present in a large percentage of re-TUR, showing a not so good performance of resection with this method. For these reasons new methodologies have been investigated in order to improve the sensitivity and specificity of WLC, such as photodynamic diagnosis (PDD), narrow band imaging (NBI), optical coherence tomography (OCT) and CT virtual cystoscopy. Some of them have been well established and supported by consistent literature while others are still to be viewed as experimental. The purpose of this review is to investigate the state of the art of these new techniques.

The incidence of small renal masses is increasing, as a result of the wide adoption of imaging exams. Their management, however, is complicated, especially in patients with decreased life expectancy or comorbidities. Approximately 20% of small renal masses are benign and, even if malignant, just 10% show aggressive pathological features. Furthermore, competing cause mortality seems to exceed the cancer-specific mortality in patients aged over 70 years. The role of percutaneous tumor biopsy is still not well defined. All these observations raise the concern as to whether surgery might represent an overtreatment for some cases of small renal masses, calling into question the role of active surveillance. The aim of this review was to evaluate the current evidence pertaining to several hot questions that need to be addressed when contemplating active surveillance for small renal masses. The most relevant publications on this subject available in the literature were selected. Five representative series of active surveillance along with the main related variables were identified. Some relevant items surrounding the field of active surveillance were identified and submitted to an evidence-based discussion. According to the recent evidence, small renal masses under active surveillance tend to show an indolent course with a low probability of disease progression, the latter being triggered most of the time by a tendency to grow faster. Unfortunately, we are currently unable to predict those few cases with aggressive behavior. According to the current evidence, active surveillance is feasible and safe in elderly and comorbid patients., (© 2012 The Japanese Urological Association.)

Objective: Leiomyomata are benign neoplasms that are rarely encountered in the genitourinary tract outside the uterus. Pathological confirmation is always needed for definitive diagnosis, in order to rule out malignancies such as leiomyosarcoma. In cases of small leiomyomata, a surveillance strategy can be suggested, although the preferred approach is complete resection. Prognosis seems to be excellent, but available data are based on few, inconsistent series, as is often the case with rare neoplasms. This article presents long-term follow-up data from the most heterogeneous series, in terms of anatomical location, currently available., Material and Methods: The present series of 33 genitourinary leiomyomata was retrieved after joining the "rare urogenital neoplasm" registry of two Italian regions. Two pathologists jointly reviewed all pathological slides and confirmed the diagnosis of leiomyoma., Results: Sixteen cases were localized to the scrotum, eight to the bladder, five to the kidney, two to the prostate, one to the urethra and one to the penis. Mean patient age was 58.4 (range 32-80) years. Mean follow-up was 15.5 (range 2-20) years., Conclusions: In this highly heterogeneous series, the disease showed excellent long-term recurrence- and progression-free interval. The accuracy of pathological diagnosis, along with the indolent long-term course, make the role of active surveillance amenable for asymptomatic cases, particularly where surgery may result in overtreatment.

Objectives: To prospectively evaluate the prognostic utility of the traditional prognostic factors and molecular markers p53 and Ki-67 in a homogeneous series of patients with non-muscle-invasive bladder cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG)., Patients and Methods: 192 intermediate- and high-risk NMIBC cases were enrolled. The variables in study were age, stage, grade, focality, tumour size, presence of associated carcinoma in situ, recurrence rate before BCG, maintenance for BCG, Ki-67 and p53. The endpoints considered were recurrence-free survival, progression-free survival, cancer-specific survival (CSS) and overall survival (OS)., Results: T stage resulted in being associated with CSS, whereas age with OS. BCG maintenance was a significantly favourable independent predictor of OS, CSS, recurrence and progression. In univariate analysis, the labelling index of Ki-67 was significantly associated with OS, CSS and progression. Multivariate analysis, however, confirmed this association only for OS. On the contrary, the labelling index of p53 was a significant predictor of recurrence, both in uni- and multivariate analyses, but with a HR inferior to 1., Conclusions: Ki-67 was an independent predictor of survival. p53 overexpression showed a significant yet inverse correlation with recurrence, thus showing little clinical utility. Age, stage and maintenance were confirmed as independent predictors of BCG response., (Copyright © 2013 S. Karger AG, Basel.)

Introduction: Primary extragonadal germ cell tumors (EGCT) are rare and it is still a matter of debate if they have to be considered as primary extragonadal issues or metastases from a primary testicular neoplasm. We describe two cases of the so-called burned-out seminoma, a primary testicular germ-cell tumor that spontaneously regressed after demonstration of retroperitoneal metastases., Cases Presentation: Two patients (35 and 50 years old, respectively) presented with CT findings of retroperitoneal masses. In both cases physical examination of the testis was not suspicious, and only scrotal ultrasound (SUS) showed parenchymal alterations such as scarring, calcifications and nodular lesions. Left orchiectomy and chemotherapy were then performed in both cases. Currently, they are both free of disease., Conclusions: Although primary germ cell tumors may be of retroperitoneal origin, the likelihood of metastasis from a testicular primary origin should always be carefully considered in order to avoid misdiagnosis and to apply the best treatment schedule for the patients. Therefore, a testicular ultrasonography is mandatory in patients presenting CT findings of retroperitoneal adenopathy, even if patients are completely asymptomatic and their physical examination appears normal.

We report the case of a sacral neurinoma, which presented with mild hydronephrosis, due to compression of the right ureter, in a 71-yr old woman admitted to our hospital with recurrent urinary tract infections. CT and MRI detected a 4 x 4 cm mass pressing on the right ureter at the sacral level, in continuity with the second sacral foramen. Given this finding, the mass was thought to be of presumable neurogenic origin. In order to both reach a conclusive diagnosis and relieve the compression of the ureter, a laparoscopic resection of the mass was performed. Surgery was successful and the pathologic examination revealed a sacral Antoni A neurinoma. Neurinomas, also called Schwannomas, are uncommon benign nerve sheath tumors arising from Schwann cells. Their diagnosis can be extremely difficult due to their aspecific symptoms and the lack of pathognomonic characteristics on imaging exams. Therefore, histopathologic evaluation is essential in establishing the diagnosis. Surgical resection seems to be the best approach, both for diagnostic and therapeutic purposes.

Unlabelled: What's known on the subject? and What does the study add? Nowadays radical prostatectomy (RP) is considered an effective treatment in high-risk prostate cancer (PCa) and the indications for a surgical approach are expanding, even in cases of very high PSA or node-positive disease. We explored the outcomes of debulking surgery in the setting of these very high-risk PCa patients, in order to assess its feasibility. This review confirms the important role achieved by surgery in the complex setting of patients with very high-risk PCA. Excellent survival rates have been reported, even when PSA exceeds 100 ng/mL. The completion of RP with lymphadenectomy might give a survival benefit in patients who were found intraoperatively to be node-positive. Furthermore, salvage RP confirmed to be the most effective treatment option after RT failure. On the contrary, up-to-date surgery of isolated nodal recurrences has shown only little benefit. Finally, there is no evidence supporting the efficacy of debulking surgery in metastatic or in hormone-refractory tumours. An accurate selection of the patient is essential., Objective: To conduct a critical analysis of the available literature on the feasibility of debulking surgery in the setting of very high-risk prostate cancer (PCa) scenarios., Patients and Methods: We performed a systematic literature search of PubMed and Embase using combinations of the following keywords: radical prostatectomy, surgery, high-risk, high PSA (prostate-specific antigen), radiorecurrent, hormone-refractory, metastatic prostate cancer, salvage. With the term 'very high-risk PCa' we indicated a clinical disease beyond the common definition of high-risk PCa, i.e. any clinical stage > T3, N0 or N+, any PSA level > 50 ng/mL and any recurrent disease after primary treatment., Results: Radical prostatectomy (RP) achieved excellent survival rates in high-risk PCa, even in patients with very high PSA level. The completion of RP with lymphadenectomy might give a survival benefit in patients who were found intraoperatively to be node-positive. Salvage RP was confirmed to be the most effective treatment option after radiotherapy failure, with increased functional outcomes and decreased side-effects in the most recent series. Surgery of isolated nodal recurrences after previous radical therapy has shown little benefit according to the few available series. There is no evidence supporting the efficacy of debulking surgery in metastatic or hormone-refractory PCa., Conclusion: Debulking surgery achieved an important role in several aggressive PCa scenarios. An accurate selection of the patient is essential., (© 2012 BJU INTERNATIONAL.)

Reduced cavernosal arterial inflow has been hypothesized to be the likely cause of erectile dysfunction after kidney transplants in recipients revascularized through end-to-end anastomosis to the internal iliac artery, suggesting that end-to-side anastomosis at the external iliac artery is preferable. The aim of this study was to prospectively evaluate the effect of the use of the external iliac artery on erectile function, hormone profiles and penile blood flow by evaluating changes in penile colour Doppler ultrasound parameters in a consecutive series of 22 recipients before and after end-to-side external iliac artery transplantation. The mean International Index of Erectile Function-Erectile Function (IIEF-EF) domain score decreased significantly 3 months after transplant (18.09±6.33 vs. 22.50±7.09, P=0.01). The reduction in peak systolic velocity (PSV) was significant for the cavernous artery homolateral to the side of transplant (42.60±18.77 vs. 52.01±19.91, P=0.01). The mean postoperative end diastolic velocity (EDV) did not differ significantly from the preoperative value (P=0.74). No statistical differences were found in the serum levels of testosterone or prolactin. Kidney grafts anastomosed at the external iliac artery produced significant (P=0.01) reductions in arterial inflow at the homolateral cavernosal artery that remained above the normal threshold. Whether these haemodynamic changes can explain the worsening of postoperative erectile function remains to be proven.

Objectives: Nowadays, ultrasound-guided percutaneous kidney biopsy (PKB) is the gold standard for renal biopsies. Nevertheless, PKB is still contraindicated by conditions such as bleeding diatheses, severe obesity, solitary kidney, uncontrolled hypertension, and previous failed attempts at PKB. In these cases, the laparoscopic approach may offer a valid and mini-invasive alternative to open biopsy. We describe our technique and report indications and outcomes of a consecutive series of retroperitoneal laparoscopic kidney biopsies (LKB)., Materials and Methods: In a retrospective review of patients who underwent LKB, we examined indications, outcomes, and complications, stratified according to the Clavien classification., Results: In all, 40 patients underwent LKB between 2001 and 2010 (mean age 58.85 years, SD 10.87). Mean serum creatinine at surgery was 3.02 mg/dL. Indications for LKB included coagulopathy (30%), polycystic kidney or multiple renal cysts (30%), solitary kidney (12.5%), and morbid obesity (10%). All the biopsies were performed with a Trucut needle. All the procedures were successful and led to pathological diagnosis. The most common pathological findings were glomerulonephritis (47.5%) and glomerulosclerosis (27.5%). All biopsies were performed in less than 1 hour. Only three complications (7.5%) were reported: two grade I and one grade IIIa according to Clavien classification. In three selected cases, we used a particular "ready-to-laparo" open surgical technique, which allowed to view a part of kidney parenchima through the 10-mm incision made for the Hasson trocar sufficient for Trucut biopsies and hemostasis under direct vision., Conclusions: This study shows that LKB is a safe, effective, and minimally invasive procedure that allows direct control of hemostasis and lower risks of postoperative morbidity compared with open biopsy. When PKB is contraindicated, LKB should be the first-choice alternative.

What's known on the subject? and What does the study add? Penile lengthening methods remain a controversial issue. Surgical procedures of "lengthening phalloplasty" are characterized by poorly defined indications and an unacceptably high rate of complications, as recently outlined by a literature review, while non-surgical techniques are largely popularized by the media but often lack scientific evidence. In the literature we found only ten articles/abstracts of studies pertaining to the topic of our review. With our review, we aimed to explore whether non-surgical methods of penile lengthening may have some scientific background. We focused specifically on penile extenders, which among conservative methods are those whose efficacy is supported by some scientific evidence. It seems that penile traction devices should be proposed as the first-line treatment option for patients seeking a penile lengthening procedure. Penile size is a matter of great interest among men who are affected by 'short penis syndrome' or just believe themselves to have a small penis, even though the dimensions of the organ fall within the normal range. Surgical procedures of 'lengthening phalloplasty' lack standardized indications and carry a high risk of complications. Several non-invasive methods of penile lengthening have been described, such as vacuum devices, penile traction devices and penoscrotal rings; even 'physical exercises' have been popularized through the media. Most of these techniques, however, are not supported by any scientific evidence. We briefly analyse the efficacy and scientific background of such non-surgical methods of penile lengthening. It seems that penile extenders represent the only evidence-based technique of penile elongation. Results achieved do not seem to be inferior to surgery, making these traction devices an ideal first-line treatment option for patients seeking a penile lengthening procedure.

A ganglioneuroma (GN) is the rarest and most benign of the neuroblastic tumors and originates from neural crest cells wherever sympathetic nervous tissue exists, such as in the retroperitoneum and adrenal gland. The diagnosis can be very challenging, given the rarity and asymptomatic presentation of this neoplasia, and can be achieved only by means of histological evaluation. Although benign, a few cases of metastatic GNs have been reported in the literature. The prognosis, however, seems to be excellent after surgical resection. We describe a rare case of multifocal retroperitoneal GN, diagnosed incidentally in a 46-year-old woman, with para-aortic and adrenal localizations. After intraoperative pathological diagnosis was made, complete excision of all the visible masses was performed. The postoperative period was uneventful and she was recurrence free 3 months after surgery. To our knowledge, this is the first case report of a multifocal retroperitoneal GN. Among the broad differential diagnoses of adrenal incidentalomas, an adrenal location of neuroblastic tumors should not be forgotten.

Introduction: Adherence to international guidelines is viewed as a prerequisite for optimal medical care delivery. Previously reported surveys for non-muscle-invasive bladder cancer (NMIBC) employed mailed questionnaires to urologists or patients resulting in conflicting degrees of agreement with existing guidelines. In the current study, contemporary information on the management of NMIBC was generated from a sample of italian centers., Patients and Methods: Eight Italian referral centers for the treatment of NMIBC were asked to collect information relative to all consecutive patients with a histology-proven NMIBC undergoing a transurethral resection from January 1 to March 31, 2009. The primary study objective was to verify the level of adherence of disease management with European guidelines., Results: 344 patients resulted in being evaluable. 49.2% of high-risk patients underwent a repeat transurethral resection. Bacillus Calmette-Guérin was employed in 35% of cases, while chemotherapy was in 22%. An early single regimen was adopted in 136 patients and only in 1 out of 3 low-risk patients. High-risk NMIBC received bacillus Calmette-Guérin and chemotherapy as first-line therapy in 66 and 12.5% respectively. After 3 months, cystoscopy had been reported for 82.5% of patients with a recurrence rate of 13%., Conclusion: Adherence of Italian Institutions to EAU guidelines was optimal when reporting baseline variables. Significant degrees of discrepancy emerged in treatment choices., (Copyright © 2010 S. Karger AG, Basel.)

Objective: Neuroendocrine bladder tumours are rare entities known for their aggressive behaviour. The aim of this study was to retrospectively evaluate the outcome of a contemporary series of 14 consecutive bladder neuroendocrine neoplasms observed at 2 institutional hospitals., Materials and Methods: The charts of patients with a pathological diagnosis of neuroendocrine bladder tumours observed at 2 institutions in the last 5 years were reviewed. Fourteen cases were retrieved. The main endpoint was to evaluate the pathological features and the cancer-specific survival (CSS) of the cohort. Subanalysis of survival based on the type of treatment received was attempted., Results: Mean age was 70.2 years. The rate of metastatic disease at diagnosis was 57.1%. Mean follow-up was 13.7 months (95% CI 5.1-22.3). The 6-month CSS rate was 57.1%, while the 2-year CSS rate was 21.4%. CSS and overall survival rates overlapped. The median survival for the cohort was 7 months. There was no statistically significant difference in survival between patients who underwent surgery and those who did not., Conclusion: Neuroendocrine bladder tumours remain a disease with an extremely unfavourable prognosis. The impact of radical surgery on survival remains questionable. Patients harbouring this rare bladder cancer should be referred for trials assessing neoadjuvant and adjuvant systemic treatment strategies., (Copyright © 2010 S. Karger AG, Basel.)

Objectives: To evaluate, in a prospective study, the diagnostic accuracy of PSA in patients with a prior negative prostate biopsy who were given finasteride for 6 months., Materials and Methods: 91 men with prior negative biopsy findings, including HGPIN and excluding ASAP, were instructed to take finasteride for 6 months. All patients were evaluated at study onset and after 6 months by clinical examination, digital rectal examination (DRE), International Prostate Symptom Score (IPSS) and National Institutes of Health Chronic Prostatitis Symptom Index (NHI-CPSI). Prostate biopsy was repeated at 6 months. PSA levels were measured at baseline and after 1, 3 and 6 months. We calculated the receiver operating characteristics (ROC) curve of PSA under the effect of finasteride for detecting prostate cancer., Results: The median PSA level decreased similarly both in those with prostate cancer and in those without findings of cancer. There was no statistically significant difference between the two groups. The areas under the ROC curve (AUC) of PSA at study onset and after 6 months of therapy with finasteride were, respectively, 0.48 (95% CI 0.36-0.61) and 0.54 (95% CI 0.42-0.66). There was no statistically significant difference between the two areas., Conclusions: The results of our study show that PSA itself has a low diagnostic accuracy for detecting prostate cancer in men with prior negative prostate biopsy findings. Finasteride does not seem to improve the accuracy of PSA in this particular population of patients.

Bladder phaeochromocytomas are rare neuroendocrine neoplasms whose diagnosis can be missed in spite of their rather suggestive presentation. It is mandatory to collect a thorough medical history and to recognize their typical symptoms. This study reports the case of a woman, treated for hypertensive crisis, who was diagnosed with bladder phaeochromocytoma thanks to a vet noting her fainting after micturition.

Context: Bacillus Calmette-Guérin (BCG) remains the most effective intravesical treatment for non-muscle-invasive bladder cancer (NMIBC), but the clinical development of BCG has been accompanied by controversy. Recent publications have called into question a number of aspects related to its use., Objective: To review the current clinical role of BCG in NMIBC, focusing on efficacy and tolerability as primary objectives and on strategies to predict response and decrease toxicity as secondary objectives., Evidence Acquisition: We performed a systematic literature search of published articles in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases for the period from 1976 to November 2008. The following "free text" combination was used in the first instance: "BCG and intravesical and bladder cancer." Further free text searches were performed by separately adding the following keywords to the combination "BCG and intravesical": survival, progression, recurrence, maintenance, dosing, toxicity, tolerability, side effects, prognostic factors., Evidence Synthesis: BCG is the most effective intravesical agent for preventing NMIBC recurrence, but its role in disease progression remains controversial. In intermediate-risk NMIBC, the superiority of BCG over chemotherapy is well established for disease recurrence but not for progression and needs to be balanced against higher toxicity. With regard to high-risk NMIBC, there is sufficient evidence to show that BCG is the most effective treatment of carcinoma in situ for ablation, disease-free interval, and progression, but the impact of BCG on the natural history of T1G3 tumors relies on a low level of evidence. Maintenance remains crucial for efficacy. The dose can be safely and effectively reduced to decrease its toxicity, which is slightly greater than chemotherapy., Conclusions: BCG should still be viewed as the most effective intravesical agent, but its role in the progression of papillary tumors needs to be clarified. BCG remains an alternative to intravesical chemotherapy in intermediate-risk NMIBC, and it is recommended as the standard of care for high-risk NMIBC., (2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

A 69-yr-old woman presented with a bulky hypogastric mass and abdominal pain. Computed tomography scan showed a mass anterosuperior and contiguous to the bladder wall, with a hypodense content, a voluminous bladder stone, and bilateral hydroureteronephrosis. Intraoperatively, the supravesical mass had the appearance of an infected urachal cyst. An unsuspected high-grade noninvasive papillary transitional cell carcinoma (TCC) of the bladder thoroughly surrounding the bladder stone became evident during the cystolithotomy. Postoperative videourodynamic study showed a normal voiding pattern with bilateral grade 4 vesicoureteral reflux. Early cystectomy was performed for uncontrolled recurrent bladder cancer, and the final pathology indicated pT1G3N0 TCC.

Haematuria in orthotopic neobladder can be due to upper urinary tract recurrence of the primary bladder tumour, the rare occurrence of a primary bowel tumour or benign conditions such as stones and infections. We report the case of a 60-year-old man with chronic hepatopathy who suffered severe bleeding from neobladder varices, which ultimately led to his death.