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The benign prostatic syndrome, comprising lower urinary tract symptomatology secondary to benign prostatic hyperplasia/enlargement, represents a major health care issue in westernized countries. The pharmacological management involves alpha-adrenoceptor antagonists, intervention into the hormonal control of prostate growth using inhibitors of the enzyme 5-alpha-reductase, and stimulation of the nitric oxide/cyclic GMP pathway by tadalafil, an inhibitor of the phosphodiesterase type 5. This review summarizes the achievements which have been made in the development of drug candidates assumed to offer opportunities as beneficial treatment options in the management of the benign prostatic syndrome. A review of the literature has revealed that the line of development is focusing on drugs interfering with peripheral neuromuscular/neuronal mechanisms (nitric oxide donor drugs, agonists/antagonists of endogenous peptides, botulinum toxin, NX-1207), the steroidal axis (cetrorelix) or the metabolic turn-over (lonidamine), as well as the combination of drugs already established in the treatment of lower urinary tract symptomatology/benign prostatic hyperplasia (phosphodiesterase 5 inhibitor plus alpha-adrenoceptor antagonist). Many research efforts have provided the basis for the development of new therapeutic modalities for the management of lower urinary tract dysfunctions, some of which might be offered to the patients in the near future.

To evaluate a novel system for MRI/TRUS fusion-guided biopsy for detection of prostate cancer (PCa) in patients with previous negative prostate biopsy and determine diagnostic accuracy when using the Prostate Imaging Reporting and Data System (PI-RADS) for multiparametric magnetic resonance imaging (mpMRI) as proposed by the European Society of Urogenital Radiology. Thirty-nine men with clinical suspicion of PCa and history of previous prostate biopsy underwent mpMRI on a 3-T MRI. In total, 72 lesions were evaluated by the consensus of two radiologists. PI-RADS scores for each MRI sequence, the sum of the PI-RADS scores and the global PI-RADS were determined. MRI/TRUS fusion-guided targeted biopsy was performed using the BioJet™ software combined with a transrectal ultrasound system. Image fusion was based on rigid registration. PI-RADS scores of the dominant lesion were compared with histopathological results. Diagnostic accuracy was determined using receiver operating characteristic curve analysis. MRI/TRUS fusion-guided biopsy was reliable and successful for 71 out of 72 lesions. The global PI-RADS score of the dominant lesion was significantly higher in patients with PCa (4.0 ± 1.3) compared to patients with negative histopathology (2.6 ± 0.8; p = 0.0006). Using a global PI-RADS score cut-off ≥4, a sensitivity of 85 %, a specificity of 82 % and a negative predictive value of 92 % were achieved. The described fusion system is dependable and efficient for targeted MRI/TRUS fusion-guided biopsy. mpMRI PI-RADS scores combined with a novel real-time MRI/TRUS fusion system facilitate sufficient diagnosis of PCa with high sensitivity and specificity.

Patients after radical cystectomy (RC) frequently complain about bowel disorders (BDs). Reports addressing related long-term complications are sparse. This cross-sectional study assessed changes in bowel habits (BH) after RC. A total of 89 patients with a minimum follow-up ≥1 year after surgery were evaluated with a questionnaire. Patients with BD prior to surgery were excluded. Symptoms such as diarrhea, constipation, bloating/flatulence, incomplete defecation, uncontrolled stool loss, and impact on quality of life (QoL) were assessed. A total of 46.1 % of patients reported changes in BH; however, only 25.8 % reported experiencing related dissatisfaction. Primary causes of dissatisfaction were diarrhea and uncontrolled stool loss. The most common complaints were bloating/flatulence and the feeling of incomplete defecation, but these symptoms did not necessarily lead to dissatisfaction or impairment in quality of life. No difference was identified between an orthotopic neobladder and ileal conduit, and even patients without bowel surgery were affected. QoL, health status, and energy level were significantly decreased in unsatisfied patients. About 25 % of patients complain about BDs after RC. More prospective studies assessing symptoms, comorbidities, and dietary habits are necessary to address this issue and to identify strategies for follow-up recommendations.

Laparoscopy introduction has dramatically changed urology. Novel techniques, such as laparoendoscopic single-site surgery (LESS) and natural orifice translumenal endoscopic surgery (NOTES), might also have substantial influence. This 2012 survey evaluated present laparoscopy use, its appraisal among urologic surgeons, laparoscopy training, and use of new techniques. Results were compared to the previous surveys, demonstrating the 10-year development of laparoscopy.A detailed questionnaire regarding demographic data, laparoscopy use, attitudes concerning laparoscopy, and novel techniques was send to 424 departments in Germany, Austria, and Switzerland. Procedures performed in 25 indications were quantitatively evaluated.The response rate was 63 % (269). Eighty-six percent of the respondents reported performing laparoscopy, compared to 54 % in 2002. Only 16 % expected economic advantages with laparoscopy, whereas 67 % expected shorter hospitalization. Seventy percent of responders anticipated comparable functional and oncological results between laparoscopic procedures and open surgery. Slow learning curves (81 %) and insufficient training facilities (32 %) were reported to impair laparoscopic surgery. On average, laparoscopic and non-laparoscopic surgical teams consisted of 2.5 and 3.5 members, respectively. LESS procedures were performed at 15 % of institutions. Twenty-two percent of respondents considered NOTES techniques valuable for future urology. Few indications (laparoscopic prostatectomies or nephrectomies) were performed frequently in specialized centers, and the rapidly increasing procedure numbers observed between 2002 and 2007 had dropped to a mild accretion. The results demonstrate broad acceptance of laparoscopy in German urologic surgery, depict the need for structured training facilities, and indicate limited impact of novel techniques (LESS and NOTES).The survey demonstrates the 10-year development of urologic laparoscopy and the broad acceptance of laparoscopic techniques.

Exact pathological staging of bladder cancer is crucial for determination of further treatment. One limiting factor is the surgical ‘incise and scatter’ technique that might contribute to tumour recurrence. En bloc resection techniques are en emerging issue. We present initial results with Thulium:YAG (Tm:YAG) en bloc resection of bladder tumours for treatment and accurate staging of solitary transitional cell carcinoma of the bladder. From June through October 2010, six patients were treated by TmLRBT (Thulium laser resection of bladder tumour). Inclusion criteria were solitary lesions, treatment naive patients and tumour localisation of the lower bladder wall and trigonum. En bloc resection was applied on all of the tumours. Two cold-cut biopsies from the tumour base were extracted. On five of the six patients, a re-resection was performed after 6 weeks. Pathological evaluation revealed 1 patient with pTa G1, 2 patients with pTa G2 and 3 patients with pT1 G3. All of the resected specimens provided detrusor muscle, and all biopsies were positive for muscle cells. No intra-, peri- or post-operative complications were observed. Bladder irrigation was mandatory in only 50% of the patients. All patients were negative for residual TCC in re-resection 6 weeks after initial treatment. TmLRBT has been proven safe and effective for both, treatment and pathological staging of primary TCC of the bladder. Tm:YAG en bloc resection therefore could be an appropriate tool for accurate staging with possibly lower scattering potential for the assessment and treatment of patients with TCC.

An impairment in the local availability of nitric oxide (NO) may impair male erectile function. The activity of l-arginine-degrading arginase enzymes may attenuate the relaxation of cavernous smooth muscle by reducing local NO production. Arginase enzymes compete with the nitric oxide synthases for the common substrate, the amino acid l-arginine. Very little data are available regarding the significance of arginase enzymes in the control of human penile erectile tissue. The aim of the present study was to elucidate the effects of drugs known to inhibit arginase activity on the relaxation of isolated human corpus cavernosum (HCC) and the production of cyclic GMP. Using the organ bath technique, the effects of the arginase inhibitors DFMO, H-Orn-OH·HCl, H-lle-OH and nor-NOHA (10 nM–10 μM) on the tension induced by NE (1 μM) and the relaxation induced by electrical field stimulation (EFS) of HCC were investigated. HCC strips were also exposed to increasing concentrations of the compounds, and the production of cGMP was determined by means of a radioimmunoassay. Only marginal effects of the arginase inhibitors were registered on the tension induced by NE and the relaxation exerted by EFS. Mean reversion of tension ranged from 18 to 8%. Only DFMO and nor-NOHA amplified the EFS-induced relaxation by 11 and 29%, respectively. These effects were not paralleled by an increase in tissue levels of cGMP. Arginase inhibitors appeared to be ineffective in reversing the adrenergic tension and increasing the electrically induced relaxation of isolated HCC.

To date, there is an increasing interest in the nitric oxide (NO) pathway as a potential pharmacological target to treat male lower urinary tract symptomatology (LUTS). In the transition zone of the human prostate, a dense nitrinergic innervation has been shown of the fibromuscular stroma, glandular epithelium and blood vessels. The expression of key proteins of the NO pathway, such as the endothelial and neuronal nitric oxide synthase (eNOS, nNOS), cGMP-degrading phosphodiesterase type 5 (PDE5) and cGMP-binding protein kinase (cGK), has also been demonstrated. The hypothesis that an impaired NO/cGMP-signaling may contribute to the pathophysiology of benign prostatic hyperplasia (BPH) is supported by the results from randomized, placebo-controlled clinical studies, indicating that NO donor drugs and PDE5-inhibitors sildenafil, tadalafil and vardenafil may be useful to treat storage and voiding dysfunctions resulting from LUTS in men. Thus, given a potential role of the NO-pathway in the prostate and/or in other parts of lower urinary tract (e.g. bladder), the enhancement of the NO signaling by NO donor drugs, PDE5 inhibitors or activators of the soluble guanylyl cyclase (sGC) may represent a new therapeutic strategy for the treatment of LUTS. This review serves to focus on the role of NO and the NO-dependent signaling in the control of smooth muscle function in the human prostate. Results from clinical trials in men with LUTS/BPH are also discussed.

Galectin-3 is a member of the glycoprotein family, actively involved in various biological interactions including cell growth, cell adhesion, cell differentiation and apoptosis. The aim of this study was to analyze the expression of galectin-3 in clear cell renal carcinoma and to assess its prognostic significance.The expression of galectin-3 was analyzed by immunohistochemistry in 149 clear cell renal carcinomas. The levels were correlated to established clinical parameters such as nuclear grade, pathological stage, lymph node, distant metastasis, and patients' survival.In normal kidney tissue, the expression of galectin-3 was found to be uniformly present in the tubular epithelial cells. A decrease of antigen expression levels were significantly associated with higher T-stages (P0.02), unfavourable long-term prognosis in univariate Kaplan-Meier (P0.007) and multivariate Cox proportional hazard analyses (P0.04). Univariate analysis could demonstrate an association with tumor-specific death with decreased galectin-3 expression, whereas multivariate analysis failed to prove the aforementioned observation.Our results suggest that a loss of galectin-3 expression is involved in renal carcinogenesis.

En bloc resection of bladder tumors (ERBT) may improve staging quality and perioperative morbidity and influence tumor recurrence. This study was designed to evaluate the safety, efficacy, and recurrence rates of electrical versus laser en bloc resection of bladder tumors.This European multicenter study included 221 patients at six academic hospitals. Transurethral ERBT was performed with monopolar/bipolar current or holmium/thulium laser energy. Staging quality measured by detrusor muscle involvement, various perioperative parameters, and 12-month follow-up data was analyzed.Electrical and laser ERBT were used to treat 156 and 65 patients, respectively. Median tumor size was 2.1 cm; largest tumor was 5 cm. Detrusor muscle was present in 97.3 %. A switch to conventional TURBT was significantly more frequent in the electrical ERBT group (26.3 vs. 1.5 %, p0.001). Median operation duration (25 min), postoperative irrigation (1 day), catheterization time (2 days), and hospitalization (3 days) were similar. Overall complication rate was low (Clavien ≥ 3, n = 6 [2.7 %]). Hemoglobin was significantly lower after electrical ERBT (p = 0.0013); however, overall hemoglobin loss was not clinically relevant (0.38 g/dl). Patients (n = 148) were followed for 12 months; 33 (22.3 %) had recurrences. In total, 63.6 % recurrences occurred outside the ERBT resection field. No difference was noted between ERBT groups.ERBT is safe and reliable regardless of the energy source and provides high-quality resections of tumors1 cm. Recurrence rates did not differ between groups, and the majority of recurrences occurred outside the ERBT resection field.

In approximately 4%-10% of patients presenting with renal cell cancer, the transluminal propagation of a tumour thrombus into the vena cava inferior or the right atrium comes to diagnosis. Recent investigations have indicated that the presence of neoplastic extension into the venous system does not reveal independent prognostic value regarding the clinical course of the disease. Although the complete surgical removal of vena cava thrombosis in patients without simultaneously occurring regional lymph node or distant metastases has become a well established treatment modality, several questions concerning this surgical strategy still remain the subject of ongoing discussions. In the present investigation that included 92 patients with renal cell cancer and intracaval neoplastic extension, it was clearly demonstrated that using cardiopulmonary bypass, deep hypothermia and circulatory arrest - preferably, during the removal of intracaval thrombosis extending into the right atrium - does not result in a substantially increased treatment-related intra- or postoperative mortality. However, in contrast to a previously reported observation, this treatment option did not reveal any substantial impact on the long-term survival of the patients following surgical therapy. Accordingly, the cranial extension of intracaval thrombosis was not identified as a biological variable of any prognostic importance for renal cell cancer patients.

Single modality bladder-sparing therapy for muscle-invasive bladder cancer, including transurethral resection (TUR), partial cystectomy, systemic chemotherapy or radiotherapy, have been demonstrated to result in insufficient local control of the primary tumour, as well as decreased long-term survival in the patients when compared to radical cystectomy. Therefore, multimodality treatment protocols that aim at bladder preservation and involve all of the aforementioned approaches have been established. Arguments for combining systemic chemotherapy with radiation are to sensitise tumour tissue to radiotherapy and to eradicate occult metastases that have already developed in as many as 50% of patients at the time of first diagnosis. It has been shown that the clinical outcome observed with this approach approximates that after radical cystectomy. Additionally, a substantial number of patients survive with an intact bladder. However, bladder-sparing approaches are costly, and require close co-operation between different clinical specialists as well as careful follow-up. The good long-term results that are observed after cystectomy and the creation of an orthotopic neobladder make the substantial advantage of a bladder preservation strategy questionable when the patient's quality of life is addressed. Additionally, bladder-sparing therapy-related side effects might result in an increased morbidity and mortality in those patients who need to undergo surgery due to recurrent or progressive disease. Multimodality bladder-sparing treatment is a therapeutic option that can be offered to the patient at centres that have a dedicated multidisciplinary team at their disposal. However, radical cystectomy remains the standard of care for muscle-invasive bladder cancer.

For clinically localized prostate cancer, recent studies strongly indicate that the determination of p53 inactivation allows the identification of a highly aggressive subgroup of prostatic tumors associated with decreased recurrence-free and long-term survival following radical prostatectomy. However, several questions regarding the determination of p53 alterations in prostate cancer, such as the poor correlation between immunohistochemistry and molecular genetic analysis, remain to be clarified. On the DNA level, p53 gene alterations have been identified in only up to 64% of tumors exhibiting immunohistochemically detected overexpression of the p53 oncoprotein. This discrepancy can be explained either by the genetic microheterogeneity of prostate cancer or by stabilization of the wild-type protein due to posttranslational events. In the present study we tried to determine the concordance between an immunohistochemically detected p53 overexpression and the result of molecular genetic analysis. Therefore, tumor tissue obtained by microdissection from 40 prostate cancer specimens was subjected to DNA-sequence analysis. Microdissection was based either only on histopathologic criteria or on the result of the immunohistochemical staining reaction. In 8 of 14 (57%) tumors a positive immunohistochemical reaction could be confirmed by DNA sequencing, which revealed a missense point mutation at the p53 gene locus, mainly in the form of G → A transversion in exon 5 of the p53 gene. Following the micropreparation of tumor cells exhibiting p53 oncoprotein overexpression, missense point mutation could be detected in an additional 4 cases. Following a microscopically guided tumor cell dissection according to the result of immunohistochemistry, DNA sequencing confirmed an immunohistochemically detected p53 overexpression in 86% of cases investigated. This result indicates that a microdissectional tumor cell preparation is recommended for molecular genetic analysis of histologically heterogeneous tissue specimens such as prostate cancer and should be performed according to and in addition to the result of immunohistochemistry when an immunohistochemical approach is available.

Paclitaxel, a natural anticancer drug, has gained widespread acceptance as an active broad-spectrum antitumor agent, including its use in urological malignancies, particularly urothelial tract cancer and testicular cancer. The mechanism of action, based on the premature stabilization of the microtubule assembly with disruption of the cytoskeletal framework, is completely different from those of DNA-damaging agents, e.g., cisplatin and ifosfamide. As a single agent, paclitaxel is one of the most active drugs in metastatic bladder cancer, with an overall response rate of 40–50% being obtained in previously untreated patients. These promising single-agent results have prompted the use of combination regimens including, in particular, cisplatin and paclitaxel. A high degree of activity for the cisplatin-paclitaxel combination as reflected by responses in 50–80% of patients, including a substantial number of complete responses (>30%), has been identified. The role of other agents such as vinorelbine, methotrexate, 5-fluorouracil, or ifosfamide as additions to this two-drug combination currently remains open. The combination of paclitaxel plus ifosfamide or vinorelbine in the absence of a platinum derivative has yielded rather disappointing results. Of particular interest may be the combination of paclitaxel and carboplatin. Both drugs can be given to patients with impaired renal function. Overall response rates of 45–60% have been reported in phase II studies. The so-called platelet-sparing effect of paclitaxel given in combination with carboplatin has resulted in a surprisingly low frequency of myelotoxicity, particularly thrombocytopenia. The combination of paclitaxel with carboplatin is being compared in an ongoing trial against the current standard MVAC regimen (methotrexate/vinblastine/Adriamycin/cisplatin) in patients with metastatic disease. Furthermore, the activity of paclitaxel-based combinations is currently being explored in the neoadjuvant setting in phase II studies, and the potential for the combination with the other new promising agent – gemcitabine – will be evalutated in a phase I setting. In prostate cancer, estramustine phosphate is widely used as palliative treatment for patients with hormone-refractory disease. In vitro synergistic activity has been observed between estramustine and paclitaxel in prostate-cancer cell lines, although paclitaxel has not demonstrated single-agent activity in patients with hormone-refractory prostate cancer. In clinical trials the combination of the two agents was associated with increased gastrointestinal toxicity. The addition of etoposide as a third drug has yielded prostate-specific antigen (PSA)-response rates of >50%, but data on quality of life and survival time have not been reported for these combinations. A true clinical role for paclitaxel in prostate cancer has therefore not been established. Paclitaxel has finally demonstrated single-agent activity in relapsed and/or cisplatin-refractory testicular cancer in recent phase II trials, indicating different mechanisms of resistance to cisplatin and paclitaxel. These results have formed the rationale for the introduction of paclitaxel as part of combination chemotherapy regimens in patients with relapsed but chemosensitive testicular cancer. Preliminary results demonstrate that paclitaxel can be safely included into these conventional-dose combination regimens. When it is used prior to high-dose chemotherapy, sufficient numbers of peripheral blood stem cells (PBSCs) for high-dose therapy can be collected. The final role of paclitaxel in risk-adapted chemotherapeutic strategies in testicular cancer is not defined, but it appears that paclitaxel-based combinations can achieve a substantial response rate in patients with relapsed disease.

Bladder cancer (BC) represents a growing health care problem worldwide. In times of tight budgets and an aging society, new strategies for the transurethral treatment of BC are needed. Laser devices used for tumor vaporization and/or en bloc resection provide an alternative to parvenu strategies. Medline/Cochrane search was performed using following terms: bladder cancer, urothelial carcinoma, laser, en bloc, vaporization, photoablation, holmium, thulium, Ho:YAG, Tm:YAG, HoLRBT and TmLRBT. Last date of search was February 12, 2014. Eighteen publications in English were identified including 800 patients (Ho:YAG = 652 patients and Tm:YAG = 148 patients). Data on en bloc resection techniques were presented in 10 publications, 7 publications provided data of tumor vaporization and one publication presented data on both. Level of evidence based on SIGN is mainly 3 (non-analytic studies); only three studies are level 2 (prospective case control studies). Tumor vaporization seems to be a promising alternative for the treatment of recurrent tumors in selected patients. It can be performed in an office-based approach without the need of general anesthesia. The use of photodynamic diagnostic might enhance surgical quality. The principle of en bloc resection should provide accurate staging in most cases; however, data on this important aspect are missing. Peri- and postoperative complications are scarce. Due to the nature of the energy source, bladder perforation caused by obturator nerve reflex is highly unlikely when using lasers. There is a trend toward decreased infield recurrence rates. Lasers are potentially useful alternatives to conventional TURBT, but systematical assessments using standardized classification systems and well-designed RCTs are needed to make results comparable.

Nephron sparing surgery for renal tumors has evolved as the standard of care for resectable renal tumors. Laparoscopic partial nephrectomy (PN) has gained recognition after technical refinements were able to match the well-established criteria for open partial nephrectomy. Laparoendoscopic surgery (LESS) is one of the approaches to further minimize invasiveness of laparoscopic surgery. We report our initial experience with LESS partial nephrectomy in single-incision transumbilical surgery technique (SITUS) in daily clinical practice. From 2010, patients undergoing SITUS-PN were prospectively evaluated. Patients with small, solitary or multiple, exophytic-enhancing renal masses were selected, whereas patients with solitary kidney, endophytic or hilar tumors were excluded. Important clinical data, PADUA and RENAL score, were assessed prospectively. Patients’ characteristics, perioperative, hematologic and pathologic data as well as pain evaluation using the visual analogue pain scale (VAPS) were assessed. A total of 13 patients underwent LESS-PN/SITUS-PN (6 right and 7 left renal units). One patient was converted to conventional laparoscopy requiring two additional ports to treat bleeding from renal vessels. Pathology revealed renal cell carcinoma in nine patients, oncocytoma in one and benign cyst in three patients. No positive surgical margin was observed. The mean blood loss was 2.1 g/dl [range 0.5–4.5 g/dl] in hemoglobin. Minimal discomfort was noted at discharge (VAPS = 0.2 ± 0.6 [range 0–2]/10]. LESS partial nephrectomy in SITUS technique is feasible for selected exophytic tumors and has been integrated into our armamentarium for nephron sparing minimally invasive surgical treatment.

The anti-androgen withdrawal syndrome (AAWS) can be seen in one-third of patients after discontinuation of first-generation non-steroidal anti-androgen therapy. With the introduction of new agents for anti-androgen therapy as well as alternate mechanisms of action, new therapeutic options before and after docetaxel chemotherapy have arisen (Ohlmann et al. in World J Urol 30(4):495-503, 2012). The question regarding the occurrence of an enzalutamide withdrawal syndrome (EWS) has not been evaluated yet. In this study, we assess prostate-specific antigen (PSA) response after discontinuation of enzalutamide.In total 31 patients with metastatic castration-resistant prostate cancer (mCRPC) underwent an enzalutamide withdrawal and were evaluated. Data were gathered from 6 centres in Germany. Patients with continuous oral administration of enzalutamide with rising serum PSA levels were evaluated, starting from enzalutamide withdrawal until subsequent therapy was initiated, follow-up ended or death of the patient occurred. Statistical evaluation was performed applying one-sided binomial testing using R-statistical software, version 3.0.1.Mean withdrawal follow-up was 6.5 weeks (range 1-26.1 weeks). None of the 31 patients showed a PSA decline. Mean relative PSA rise over all patients was 73.9 % (range 0.5-440.7 %) with a median of 44.9 %.If existent, an AAWS is at least very rare for enzalutamide in patients with mCRPC after taxane-based chemotherapy and does not play a clinical role in this setting. This may be attributed to the different pharmacodynamics of enzalutamide. Longer duration of therapy or a longer withdrawal interval may reveal a rare EWS in the future.

Percutaneous renal surgery (PRS) is a challenging procedure for urologic surgeons and requires a large variety of different skills. Our objective was to improve the preexisting porcine kidney-training model for percutaneous renal access and PRS.For our biologic training model, we use porcine kidneys with preserved ureter. The ureter was dissected, stones were placed into the collecting system using a 16, 5F Amplatz sheath, and a 12Ch indwelling catheter was placed in the ureter for further irrigation with blue-dyed saline. The kidney was placed between two porcine full-thickness skin lobes in an existing laparoscopy trainer (SITUS Box). The kidney was punctured with ultrasound guidance, and minimally invasive percutaneous nephrolithotomy (MIP) was then performed as previously described. The model was evaluated in MIP training courses, which are regularly held at the Hannover Medical School.All trainees were urologists with experience in endourologic surgery. Eleven participants were trained in this model. Percutaneous puncture under ultrasonographic guidance and following intrarenal surgery was successful in all 11 (100 %) cases. Therefore, all participants rated the model useful for simulating percutaneous renal surgery.Compared to recently published models, this new porcine kidney model is easy to prepare and is cost-effective by using standard material. Moreover, it provides realistic and reproducible practice for PRS in the laboratory. Unfavorably, the described organ model requires an existing laparoscopy training system. Comprehensively, the presented organ model approximates the natural retroperitoneal circumstances precisely by using the two full-thickness skin flaps with the fatty subcutaneous tissue.

Experimental studies have provided the basis for the evaluation of inhibitors of the phosphodiesterase type 5 (PDE5) in the treatment of lower urinary tract symptomatology (LUTS) secondary to benign prostatic hyperplasia (BPH). It has been speculated that the clinical efficacy of PDE5 inhibitors in patients with LUTS/BPH can be explained by their effects on the urinary bladder rather than on the prostate. Hence, the significance of the nitric oxide (NO)/cyclic GMP signaling in the control of the human prostate requires further clarification.The present study aimed to investigate by means of immunohistochemistry in the human prostate the expression and distribution of key mediators of the NO pathway, namely cyclic GMP, the neuronal nitric oxide synthase (nNOS), and cyclic GMP-binding protein kinases type I (cGKIα, cGKIß), in relation to PDE5, protein kinase A (cAK), and the vasoactive intestinal polypeptide (VIP).In the smooth muscle portion of the transition zone, immunosignals specific for the PDE5 were found co-localized with cyclic GMP, cGKIα, and cGKIß, as well as with the cyclic cAMP-binding protein kinase A. Smooth muscle bundles were seen innervated by slender varicose nerves characterized by the expression of nNOS. Some of these nerves also presented staining related to the neuropeptide VIP.The findings give hints that the cyclic GMP- and cyclic AMP-dependent signal transduction may synergistically work together in regulating muscle tension in the transition zone. This might be of significance for the identification of new pharmacological avenues to treat patients with symptomatic BPH.

Bladder cancer is the second most common malignancy of urologic tumors. Back in 1976, lasers were added to the endourological armetarium for bladder tumor treatment. Despite nowadays’ standard procedure for staging and treating non-muscle invasive bladder tumor by transurethral resection of bladder tumors (TURB) via a wire loop, laser resection techniques for bladder tumor came back in focus with the introduction of Ho:YAG and not to mention recently Tm:YAG lasers. This review aims to display the current evidence for these techniques. Throughout April 2010, MEDLINE and the Cochrane central register of controlled trials were searched previously for the following terms: “Laser, resection, ablation, coagulation, Nd:YAG Neodym, HoYAG: Holmium, Tm:YAG Thulium and transitional carcinoma, bladder, intravesical.” Eleven articles on Ho:YAG and 7 on Tm:YAG were identified. Searches by Cochrane online library resulted in no available manuscripts. Today, Nd:YAG does not play any role in treatment of lower urinary tract transitional cell carcinoma. Ho:YAG and Tm:YAG seem to offer alternatives in the treatment of bladder cancer, but still to prove their potential in larger prospective randomized controlled studies with long-term follow-up. Future expectations will show whether en bloc resection of tumors are preferable to the traditional “incise and scatter” resection technique, in which is contrary to all oncological surgical principles. For the primary targets, here are within first-time clearance of disease, in addition to low in-fields and out-of-fields recurrence rates.

The present contribution analyses long-term data regarding oncological, functional, and quality of life aspects of patients subjected to cystectomy due to malignancy with subsequent orthotopic bladder substitution. A literature search was conducted to review literature published from 1887 until today. Oncological aspects, special considerations on female patients, quality of life, geriatric patients, and impact of minimally invasive surgery were also addressed and discussed. After more than three decades, orthotopic bladder substitution subsequent to radical cystectomy has stood the test of time by providing adequate long-term survival and low local recurrence rates. Compared to radical cystectomy, neither radiation nor chemotherapy, nor a combination of both, offer similar long-term results. Orthotopic bladder substitution does not compromise oncological outcome and can be performed with excellent results regarding functional and quality of life issues. Chronological age is generally not a contraindication for cystectomy. Orthotopic bladder substitution should be the diversion of choice both in men and in women, whenever possible. For orthotopic urinary diversion, a careful patient selection considering tumor extent, patient motivation, preoperative sphincter function, other local and systemic adverse confounding factors, and overall life expectancy must be taken into account. Minimally invasive techniques are promising concepts for the future, awaiting confirmation in larger patient cohorts.

Ficarra et al. (Eur Urol 56:786-793, 2009) published a preoperative anatomical classification (PADUA) to assess the impact of anatomical parameters of renal tumors on complication rate of nephron-sparing surgery (NSS). The objective of this study is to provide a bi-center external validation of this classification using the technique of hilar arterial clamping during open and laparoscopic NSS and to correlate the PADUA score to the ischemia time.240 consecutive tumors treated with open and laparoscopic NSS were reclassified according to the PADUA classification. Complications were graded according to the modified Clavien system (Dindo et al. in Ann Surg 240:205-213, 2004). Chi-square tests and multivariate logistic regression models addressed the predictive value of PADUA classification on overall complication rate and grade.Mean patient age was 62.2 +/- 13.3 years. Eastern Cooperative Oncology Group performance was 0 in 76%, 1 in 22% and 2 in 2%. 61 (25%) were treated laparoscopically. The median PADUA score was 7.5 (range 6-13). Mean surgery and ischemia time was 189 +/- 95 and 24 +/- 22 min, respectively. Overall complication rate was 23% (n = 54). On univariate analysis, the PADUA score correlated with complication rate (p0.001) of open and laparoscopic NSS. On multivariate, only the PADUA score correlated with complication rate (p = 0.0056). Ischemic time correlated with the PADUA score and was significantly higher in PADUA scoreor = 10 (p = 0.034).The PADUA score is a reliable tool to preoperatively predict the risk of complications. In addition, it might be beneficial for a more objective patient selection for laparoscopic surgery and teaching NSS.

To assess the specific impact of urinary collecting system (UCS) invasion on the long-term prognosis of patients with renal cell carcinoma (RCC). We evaluated 1,678 patients with complete information about UCS invasion of their primary RCC who had undergone renal surgery between 1990 and 2005 in two high volume centers (MH Hannover and Marburg, Germany); the mean follow-up was 5.4 years. Hundred and forty-nine (8.9%) patients demonstrated collecting system invasion. These patients incurred a significant increase in the likelihood of cancer-related death (HR 1.7, 95% CI: 1.4–2.0; P

Purpose Urocortin (Ucn) exerts its actions through activation of two corticotropin-releasing factor receptors (CRFRs), CRFR1 and CRFR2. Involvement of Ucn/CRFR2 system in pathophysiological conditions such as the regulation of angiogenesis and inhibition of proliferation has been already reported. Suppression of neovascularization through reduction of vascular endothelial growth factor and inhibition of tumor cell cycling is modulated mainly through activation of CRFR2. To find out a possible involvement of Ucn/CRFR2 in kidney tumor, we examined the expression of Ucn and CRFR2 in normal and tumoral kidney specimens. Methods We applied reverse transcriptase PCR (n = 14), immunofluorescence (IF) on tissue microarrays (n = 25) and confocal microscopy to examine the mRNA expression and peptide/protein localization of Ucn and CRFR2 in normal kidney versus clear cell renal cell carcinoma, respectively. Results Ucn and CRFR2 mRNAs are expressed in normal and tumor specimens. In normal tissue, IF showed a cytoplasmic staining of Ucn mainly in proximal tubules, whereas a diffuse nuclear staining with diverse intensity was observed in tumoral tissues. CRFR2 was detected in proximal tubules and vasculature of normal specimens. Intriguingly, an almost complete loss of CRFR2 was observed in epithelial cells and microvessels within tumor tissues. Conclusions Here, and for the first time, we show the expression of Ucn and CRFR2 in human kidney and renal cell carcinoma. We propose that the nuclear translocation of Ucn along with the loss of CRFR2 in epithelial cells and microvasculature of tumoral specimens may be involved in the pathobiology of renal cell carcinoma.

Retroperitoneal lymph node dissection (RPLND) is still the most sensitive and specific method for the detection of lymph node metastases in stage I nonseminomatous testicular carcinoma. In stage II disease, residual malignant tumor and mature teratoma can be removed. Acceptance of this operation, however, has decreased due to the morbidity caused by the open approach. To reduce this morbidity, and to improve the acceptance of RPLND, laparoscopy has been introduced. Clinical data with long-term follow-up are now available which demonstrate the technical feasibility of laparoscopic RPLND. Studies comparing laparoscopy and open surgery show advantages for the laparoscopic approach in terms of reduced blood loss, intraoperative complications and operative time. Mainly minor complications, such as chylous ascites or lymphocele formation, are observed. The conversion rate to open surgery, mainly due to intraoperative bleeding, is acceptable at less than 10%. As in open surgery, antegrade ejaculation can be preserved successfully. RPLND has also been shown to provide adequate oncological results. In stage I disease, lymph node metastasis is found in 25-41% of cases. Patients with histologically proven retroperitoneal tumor receive adjuvant chemotherapy whereas individuals without evidence of retroperitoneal disease do not require additional treatment. Follow-up controls in both groups, without local recurrence, demonstrate the excellent diagnostic accuracy of this procedure. Meanwhile laparoscopic RPLND has also been introduced successfully in the management of stage II disease. Small volume residual tumors can be removed with an acceptable complication rate. However, this operation is technically demanding and should be performed only at institutions with considerable laparoscopic experience. In conclusion, laparoscopic RPLND is a safe method for low-stage germ cell tumors with minimal invasiveness and excellent clinical results. Thus laparoscopy might contribute to a better acceptance of RPLND.

Results from basic research scrutiny indicate a role for non-adrenergic, non-cholinergic transmitters, among which there are various peptides, in the physiology of normal male sexual function. Nevertheless, it is not yet known which particular peptides are essentially involved in maintaining sexual arousal and regulating penile tumescence and rigidity in adult males. Vasoactive intestinal polypeptide (VIP), a peptide with smooth muscle relaxing properties, is considered to be one of the factors that contributes to such control. The present study was performed to evaluate the significance of VIP in normal male sexual function. We determined the plasma levels of VIP in the systemic and cavernous blood of 54 healthy adult male volunteers, who were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and erection. Whole blood was aspirated from the corpus cavernosum and the cubital vein during penile flaccidity, tumescence, rigidity and detumescence, and VIP was quantified in plasma aliquots by means of a radioimmunoassay. Of the 54 volunteers, 16 were permitted to masturbate and ejaculate, and blood was then again withdrawn from the cavernous meshwork and the cubital vein in order to measure VIP. All VIP levels were registered within the normal physiological range from 3.0-30 pmol/l. No increase in median VIP plasma levels was observed in the systemic and cavernous blood when the flaccid penis became rigid. During penile detumescence, mean cavernous VIP level increased to 11.9+/-7.8 pmol/l (baseline: 8.6+/-3.0 pmol/l), whereas VIP remained unaltered in the systemic circulation. Following ejaculation, mean VIP level in the cavernous blood was elevated to 25.3+/-10.9 pmol/l, whereas, in the systemic blood, no significant changes were registered. Our results support the hypothesis that VIP plays a functional role in the mechanism of male sexual arousal. Nevertheless, our data indicate that the peptide is not the main non-adrenergic, non-cholinergic mediator of penile tumescence and rigidity in human males.

Recent results demonstrate an emerging role for paclitaxel in patients with urothelial-tract cancer and in patients with testicular cancer. Yielding response rates in the range of 40-50% as a single agent, paclitaxel is one of the most active drugs in metastatic bladder cancer. Ongoing trials of paclitaxel combination chemotherapy with cisplatin or cisplatin and ifosfamide demonstrate substantial objective remission rates above 70% and, in addition, a high range of complete responses. Thus, paclitaxel appears to be an important drug when used as part of first-line combination chemotherapy for metastatic bladder cancer. Ongoing clinical trials focus on the combination of paclitaxel with cisplatin, ifosfamide, gemcytabine, and carboplatin. Furthermore, paclitaxel administration has been demonstrated to be easily applicable to patients with reduced renal function, requiring no dose reduction and producing no increase in toxicity. Future strategies will have to compare the most active paclitaxel combination regimen with first-line MVAC (methotrexate, vinblastine, adriamycin, cisplatin) chemotherapy. Finally, the role of paclitaxel combination regimens needs to be explored in the adjuvant and neoadjuvant setting in patients with bladder cancer. In testicular cancer, paclitaxel has initially been tested in patients with cisplatin-refractory disease. Among 4 consecutive trials involving a total of 83 patients a response rate of 26% has been observed using dose schedules varying from 3-h to 24-h infusions and doses ranging from 175 to 250 mg/m2. The major toxicities of paclitaxel include neutropenia, neurotoxicity, and fatigue syndrome. Currently, combinations of paclitaxel with cisplatin +/- ifosfamide are used as first- or second-line salvage therapy in patients with relapsed metastatic testicular cancer. The German Testicular Cancer Study Group uses a paclitaxel (Taxol, ifosfamide, cisplatin; TIP) combination regimen as salvage treatment. Following the TIP regimen and the application of granulocyte colony-stimulating factor (G-CSF), peripheral blood stem cells (PBSC) are harvested and the patients subsequently receive high-dose chemotherapy with PBSC rescue. Since only a few drugs have demonstrated substantial activity in cisplatin-refractory disease, paclitaxel will be used in early salvage strategies and, possibly, as first-line chemotherapy as a part of platinum-based combination regimens in patients with testicular cancer. Further trials confirming the important role of paclitaxel in this highly curable malignancy and a thorough investigation of its acute and long-term toxicity will be the future tasks.

Surgical removal continues to be the mainstay in the treatment of renal-cell carcinoma with neoplastic venous extension. The steady improvement of surgical and anesthesiological techniques and the introduction of complete circulatory arrest has dramatically improved the morbidity even of patients with extensive thrombi. If ultrasound or computerized tomography (CT) scanning suggests the presence of a venous extension in a patient with renal-cell carcinoma, cavography, magnetic resonance imaging (MRI), transesophageal color-coded ultrasound, and echocardiography may be needed to resolve the questions of cranial extension and vascular wall infiltration. Surgical stratification and, thus, classification of the venous extension depend on the potential need for complete circulatory arrest. Surgical removal is done en bloc for smaller venous extensions and in a two-step procedure (radical nephrectomy followed by thrombectomy) for more extensive thrombi. In patients with infiltration of the suprahepatic inferior vena cava, the hepatic veins or atrium, pending thrombotic embolism, or large masses of suprahepatic thrombotic material, the use of cardiopulmonary bypass and complete circulatory arrest is recommended.

To spare organ function, partial resection of early diagnosed renal-cell carcinoma (RCC) is applied for well-localized and small-volume RCC with increasing frequency, although recurrence of the tumor in the same kidney is occasionally observed. The aim of the present study was to establish objective prognostic parameters that would allow the selection of tumors suitable for an organ-saving procedure. Of the 160 patients undergoing a radical nephrectomy, 67 were included in this study. In 7/45 patients with lymph-node dissection (15.6%), clinical staging revealed a false-negative lymph-node status. By means of conventional histopathology, multifocality could be demonstrated in 2/67 patients (3%); in 1/67 patients (1.5%), the ipsilateral adrenal gland was unexpectantly tumor-involved. Both tumor tissue and normal peritumoral tissue were examined for the presence of premalignant and tumor cells on the basis of DNA ploidy and of the expression of the tumor-associated G250 antigen, which is specifically expressed at the surface of renal cancer cells. In 40/67 (59.1%) peritumoral tissue specimens, cells with an abnormal DNA content could be observed using automated image analysis. In 12/67 cases (18%), cells obtained from peritumoral tissue also showed an aneuploid DNA histogram; 4/67 (6%) had a tumor-correlated DNA ploidy. Additionally, 38/67 (56.9%) of these tissues, histopathologically classified as normal, contained cells expressing the G250 antigen. These observations were independent of the stage or histological grade of the tumor. These data indicate that classic pathological parameters for tumor staging are insufficient for the detection of multifocality, occurring in more than 15% of cases. Additionally, it was shown that examination of tissue adjacent to the RCC allowed a specific detection of abnormal cells revealing abnormal ploidy or altered expression of tumor-associated antigens as compared with normal renal tissue in nearly 60% of cases investigated. The clinical relevance of this observation remains to be determined.

For a variety of human malignancies such as breast cancer and cancer of the prostate, p53 oncoprotein overexpression indicating an alteration of the p53 tumorsuppressor gene has been described as a prognostic factor for a poor clinical outcome. To investigate the overexpression of p53 oncoprotein in transitional-cell carcinoma of the bladder, 58 bladder cancer specimens of different clinical stages and histological grades were investigated using an immunohistochemical approach. A correlation between p53 positivity and tumor stage was observed, with an increase from 38.5% of superficial (Ta) tumors to 83.3% of muscle-invasive (T3/T4) tumors staining positively for p53 oncoprotein. Furthermore, an increase from 46.7% of G1 tumors to 75% of G3 tumors was observed. In 22 of 25 (87%) informative patients the results of the immunohistochemical staining could be verified by the determination of p53 mutations as detected by polymerase chain reaction (PCR)-directed analysis of restriction-fragment-length polymorphisms (RFLP). To determine the prognostic value of p53 immunohistochemistry for the clinical course of superficial bladder cancer, the overexpression of p53 oncoprotein was investigated in 41 patients with superficial bladder tumors (T1) undergoing complete transurethral tumor resection. The detection of p53 protein was correlated with further clinically important variables such as sex, age, histological grading, former instillation therapy, and immunohistochemical determination of the proliferation rate by staining for PCNA (proliferating-cell nuclear antigen; monoclonal antibody PC10). After a median follow-up period of 54 months, 7 of 8 patients for whom more than 20% of cells stained positively for p53 had disease progression as compared with only 1 of 33 patients who were negative for p53 detection (P