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Purpose: To assess long-term clinical and oncological outcome in women undergoing radical cystectomy and ileal neobladder reconstruction for invasive bladder cancer., Methods: From 1995 to 2010, a total of 121 women with clinically organ-confined urothelial carcinoma underwent radical cystectomy with an orthotopic ileal neobladder. Median follow-up was 56 months. Clinical course, functional, pathological, and oncological outcome of these women were analyzed., Results: Seventy-six patients (62.8%) experienced a complication of some type within 90 days of the procedure. 56 patients (46.3%) experienced minor complications, whereas 20 patients (16.5%) experienced major complications. Pathological subgroups included 70 patients (57.9%) with organ confined, lymph node-negative tumors, 24 (19.8%) with extravesical, lymph node-negative disease and 27 (22.3%) patients with lymph node-positive disease. The 5-year overall survival rate in patients with organ-confined (≤pT2, pN0), locally advanced (≥pT3, pN0), and metastatic disease was 80.2%, 81.9%, and 45.1%, respectively. 4 women (3.3%) experienced a local (pelvic) recurrence. One patient presented with a urethral recurrence (0.8%). Daytime and nighttime urinary continence (0-1 pad) was reported by 82.4 and 76.5%, respectively. Clean intermittent self-catheterization was required by 58.0%. The retrospective study design was the major limitation of the study., Conclusions: Despite a considerable complication rate, radical cystectomy with orthotopic diversion in female patients with bladder cancer may be considered a standard therapeutic option for selected patients with excellent oncological outcome including a low incidence of local and urethral recurrence.

The idea of modern palliative care goes back to the times of Dame Cicely Mary Strode Saunders in 1967, a British nurse and physician. Modern palliative care is a multimodal therapeutic and supportive concept for the patient, when curative care has failed or seems to be not reasonable. In this article we review the basics of current palliative care and focus in particular on specific medicamentous therapy during the final episode of life., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: As life expectancy is increasing the incidence and therefore the number of elderly female patients with bladder cancer is also increasing. The aim of this study was to assess long-term clinical, functional and oncological outcome in elderly women (≥70 years) who were treated by radical cystectomy and ileal neobladder reconstruction for invasive bladder cancer., Material and Methods: A total of 121 women with clinically organ-confined invasive urothelial carcinoma underwent radical cystecomy with an orthotopic ileal neobladder in Ulm between 1995 and 2010. The clinical course, functional, pathological, and oncological outcome of these women were analyzed retrospectively and compared between patients ≥70 (n=24) and <70 years of age (n=97). All complications which occurred during the first 90 days after surgery were analyzed in detail, defined and classified according to the modified Clavien system., Results: The overall 90 day complication rates were 66.7 % and 62.5 % for patients ≥70 and <70 years, respectively. Of these 54.2% and 44.8% were minor complications and 12.5 % and 17.7 % were major complications, respectively. Infections were the most frequent cause of complications with 36.7 %. Univariate analyses revealed that neither age nor comorbidity (ASA score) were significant predictors of perioperative complications. The daytime continence rates were comparable in both age groups (71% versus 82%, p=0.64); however, younger patients showed significantly higher night time urinary continence rates (43% versus 89%, p=0.013). Neither univariable nor multivariable analyses indicated that age ≥70 years had a significant impact on tumor-specific survival., Conclusions: Chronological age per se does not seem to be a contraindication for the creation of an orthotopic ileal neobladder; however, the risk of postoperative incontinence seems to increase with age.

Objective: The risk of local recurrence after radical prostatectomy (RP) is considerably dependent on local tumor stage. To improve local staging, the aim of this study was to assess the feasibility of quantitative methylation-specific PCR (Q-MSP) for the identification of promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1) to detect occult prostate cancer (PCa) cells in the prostatic fossa after RP., Methods: A total of 39 consecutive patients with clinically organ-confined PCa underwent RP. After gland excision, biopsies were obtained from eight defined areas of the prostatic fossa and bisected for both histopathological and molecular analyses. Results were related to clinicopathological data including tumor stage, Gleason score, prostate-specific antigen (PSA), and biochemical recurrence., Results: Of 39 patients, 11 with PCa had at least one positive molecular margin status indicated by GSTP1 methylation. These included 5 of 17 (29.4%) with organ-confined and 6 of 22 (27.3%) with advanced (≥pT3 and/or pN+) PCa. GSTP1 methylation in surgical margins strongly correlated with histopathological R-status (P = 0.022) and preoperative PSA (P = 0.01) whereas no association with tumor stage (pT2 vs pT3), grade (Gleason score <7 vs ≥7), and lymph node status was found. No patient experienced biochemical relapse., Conclusions: GSTP1 hypermethylation detected by Q-MSP in prostatic fossa biopsies after RP is well suited for the detection of occult tumor cells in surgical margins. However, the limited number of patients and the short-term follow-up does not allow definite conclusions on the prognostic value of GSTP1 in surgical margins.

Purpose: A recently identified mechanism allowing prostate cancer (PCa) cells to grow in the absence of androgens is the expression of constitutively active, C-terminally truncated androgen receptor (AR) variants lacking vast parts of the ligand-binding domain. These AR variants termed ARΔLBD are either products of alternative splicing, point mutations leading to premature stop codons or proteolytic cleavage of the AR. Some controversies exist about the requirement of additional full-length AR for the full transcriptional activity of the ARΔLBD. On basis of a mutated, C-terminally truncated AR termed Q640X, we developed an experimental model for the study of ARΔLBD in PCa cells., Methods: Activation of AR-dependent promoters was analyzed by reporter gene assays. Dimerization studies were conducted using a mammalian two-hybrid system., Results: Although Q640X/Q640X homodimers were able to induce the expression of certain AR target genes, Q640X/AR heterodimers were necessary to activate the full panel of androgen-dependent genes under androgen-deprived conditions., Conclusions: The following study supports the hypothesis that castration-resistant prostate cancer (CRPC) cells are able to activate specific androgen-dependent genes by selective modulation of the ratio between ARΔLBD and their putative dimerization partners like the full-length AR or other ARΔLBD in the absence of androgens. The present data suggest that AR-mutant Q640X is a powerful experimental tool for the functional analysis of ARΔLBD in CRPC.

Objective. To evaluate and compare noncontinent and continent urinary diversion after radical cystectomy in patients with bladder cancer. Methods. A total of 301 patients submitted to radical cystectomy at the Charité-University Hospital Berlin from 1993 to 2007 including 146 with an ileal conduit and 115 with an ileal neobladder. Clinical and pathological data as well as oncological outcome were retrospectively analyzed and compared. Quality of life was analyzed using the EORTC QLQ-C30 and BLM30 questionnaires. Results. 69.1% and 69.6% of all patients who received an ileal conduit and ileal neobladder, respectively, developed early complications. The two groups differed significantly concerning the occurrence of postoperative ileus (P = 0.02) favoring patients who received an ileal conduit but not with regard to any other early-onset complication evaluated. Patients with ileal neobladder had a significantly better global health status and quality of life (P = 0.02), better physical functioning (P = 0.02), but also a higher rate of diarrhoea (P = 0.004). Conclusion. Cystectomy with any type of diversion remains a complication-prone surgery. Even if the patient groups are not homogeneous in all respects, there are many arguments in favor of the ileal neobladder as the urinary diversion of choice.

Objective. To evaluate functional outcome of the retrourethral transobturator sling suspension (RTS) in the treatment of stress urinary incontinence (SUI) caused by prior prostate surgery. Methods. The RTS (AdVance male sling) was implanted in 32 patients who suffered from mild to severe postsurgical-treatment incontinence at the University Hospital Ulm from September 2010 to September 2011 including 10 patients with prior radiation therapy. Functional data (uroflowmetry, daily pad use, and postvoid residual urine) as well as quality of life with impact of urinary problems (ICIQ-UI SF) were prospectively assessed at baseline and during followup. Results. After a median followup of 9 months (range, 3-14) the incontinence cure rate (no pad usage) was 56.2% and the improvement rate (1-2 pads/day or ≥50% reduction) was 21.9%. No improvement was observed in 21.9%. Daily pad use and ICIQ-UI SF score improved significantly. No major perioperative complications occurred. Postoperatively, 15.6% of the patients exhibited transient acute urinary retention which resolved without further treatment after a maximum of 3 weeks. One patient underwent sling explantation due to dislocation and persistent perineal pain. Conclusions. The implantation of the RTS is a safe and effective procedure in selected patients with SUI resulting from prostate surgery.

The choline-positron emissiontomography / computed tomography (choline-PET / CT) is a widely used imaging method for prostate cancer. This review concentrates on the relevance of choline-PET / CT for primary diagnosis, staging and re-staging of prostate cancer and highlights possible -applications in clinical practice. Therefore, we performed a systematic literature research via Pubmed and Medline database for original articles, reviews and editorials on choline-PET / CT and prostate cancer. Choline-PET / CT should not be routinely used for primary diagnosis of prostate cancer due to a lack of data. With regard to the definition of the local tumour extent (T-stag-ing) choline-PET / CT plays only a minor role, in contrast, for the evaluation of lymph node involvement it has a high positive predictive value and is equal to conventional scintigraphy in detecting bone metastases. Moreover, in cases of biochemical relapse following local therapy, choline-PET / CT seems to be appropriate for differentiating between local recurrence and systemic prostate cancer metastasis, particularly when patients are selected by defined criteria (PSA value > 1.0  ng / mL and / or PSAdt < 6  months and / or Gleason score > 7 and / or primary radiotherapy). The non-critical routine use of choline-PET / CT for patients with prostate cancer cannot be recommended, and this not only because of its high costs. It should be applied to definite clinical questions after thorough selection of appropriate patients., (© Georg Thieme Verlag KG Stuttgart ˙ New York.)

Cancer is the second most common cause of death in women of childbearing age. However, renal cell carcinoma (RCC) is a rare tumor in this collective with an incidence far below 5/100,000 cases per year. Therefore, medical experience with respect to diagnostics and therapeutic management of newly diagnosed RCC in pregnant women is scarce and the number of published cases low. However, recent studies indicated that higher estrogen levels and multigravidity could be associated with a higher risk of RCC. The aim of this article is to summarize the clinical experience in treating pregnant women with renal cancer against the background of those cases published in the literature.

Objectives: Obesity increases the risk of developing renal cell carcinoma (RCC). We assessed whether different body mass index (BMI) levels and the body surface area (BSA) at the time of surgery had an effect on aggressiveness and long-term prognosis of RCC., Methods: The study included 1,595 RCC patients with complete information about their BMI who had undergone surgery for renal cell cancer at the University Hospitals in Hannover (MHH) and Marburg between 1990 and 2005. The mean follow-up was 5.0 years., Results: A higher BMI and a higher than average BSA were significantly associated with younger age. A high BMI value was additionally related to a lower tumor grade, the clear cell histological subtype, and metastasis at the time of diagnosis. Overweight patients had a significantly lower risk of cancer-related death; their median 5-year tumor-specific survival rate was 76.9% (BMI>30) and 72.6% (BMI 25-30) as opposed to 63.5% for patients with a BMI below 25 (p<0.001). However, the positive correlation between a high BMI and tumor-specific survival could be confirmed in multivariable analyses for localized clear cell RCC only., Conclusion: We identified BMI as an independent prognostic marker of improved cancer-specific survival in patients with RCC, particularly with organ-confined clear cell cancer.

Orthotopic neobladder reconstruction is an established treatment option in female patients undergoing radical cystectomy for invasive bladder cancer. Long-term results have proven its oncological safety and functional efficacy in both organ-confined and locally advanced disease. The use of nerve-sparing procedures has the potential to further improve the functional results in terms of postoperative continence and sexual function as long as we adhere to basic oncological principles. One important contraindication for performing neobladder reconstruction in female patients with bladder cancer is a positive urethral margin at radical cystectomy. In this respect, frozen section analysis is associated with a high sensitivity and specificity for the detection of positive urethral margins. The risk of urethral recurrence at 5 years in patients with negative urethral margins at cystectomy is ≤ 1 % and may become clinically apparent as inguinal lymphadenopathy due to changes of the lymphatic drainge after neobladder reconstruction. The 5-year recurrence-free survival after neobladder reconstruction in female patients with organ-confined bladder cancer ranges between 63 and 75 %. In female patients with locally advanced node-negative disease (≥ pT3a-4a, pN0) who underwent an orthotopic neobladder the recurrence free survival at 5 years is 71 % and so does not significantly differ from that of female patients with node-positive disease treated with an cutaneous diversion. Whether robotic cystectomy has the potential to further improve the functional outcome after neobladder reconstruction in female patients and achieve oncological long-term results comparable to those of open series is still under investigation should further be evaluated in prospective trials., (© Georg Thieme Verlag KG Stuttgart ˙ New York.)

Background: Meta-analysis evaluating the accuracy and sensitivity of FDG (2-[(18)F]-fluoro-2-deoxy-D-glucose) positron emission tomography (PET) to predict viable residual tumours in patients with metastatic seminoma., Material and Methods: Altogether 5 studies with 130 patients were identified. Both FDG PET and the size of the residual lesions on conventional computed tomography (CT; lesions either ≤ or > 3 cm) were correlated with the presence or absence of viable residual tumour., Results: The specificity (92 vs 59%), sensitivity (72 vs 63%), positive (70 vs 28%) and negative (93 vs 86%) predictive value of FDG PET were superior to data obtained by assessing residual tumour size (either ≤ or > 3 cm) applying CT scans alone., Conclusion: In view of the data currently available, FDG PET seems to be a clinically useful predictor of viable tumour in post-chemotherapy residuals of pure seminoma.

Purpose: Sarcosine in prostate cancer tissue samples was recently reported to be increased during prostate cancer progression to metastasis and suggested to be a key metabolite of cancer cell invasion and aggressiveness. We reevaluated sarcosine in prostate cancer tissue samples as a potential indicator of tumor aggressiveness, and as a predictor of recurrence-free survival., Materials and Methods: Sarcosine in matched samples of malignant and nonmalignant tissue from 92 patients with prostate cancer after radical prostatectomy was measured in the framework of a global metabolite profiling study of prostate cancer by gas chromatography/mass spectrometry. We related results to age, prostate volume, tumor stage, Gleason score, preoperative prostate specific antigen and biochemical recurrence, defined as a persistent prostate specific antigen increase of greater than 0.2 ng/ml. Nonparametric statistical tests, ROC curves and Kaplan-Meier analyses were done., Results: Median sarcosine content in tissue was about 7% higher in matched malignant vs nonmalignant samples, which was significantly. Sarcosine values were not associated with tumor stage (pT2 vs pT3), tumor grade (Gleason score less than 7 vs 7 or greater) or biochemical recurrence. The lack of metastatic tissue samples was a study limitation., Conclusions: Sarcosine in prostate cancer tissue samples cannot be considered a suitable predictor of tumor aggressiveness or biochemical recurrence., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Transperitoneal radical cystectomy with intraperitoneal ileal neobladder is the standard surgical treatment for muscle-invasive bladder cancer. To reduce morbidity, we established in 2002 an extraperitoneal approach including extraperitonealization of the ileal neobladder. This retrospective study compares the results of the two procedures with a focus on the peri- and postoperative course., Methods: Ninety-five male patients with invasive urothelial cancer who underwent radical cystectomy with ileal neobladder at our hospital from January 1998 to May 2007 were analyzed. Forty-seven patients underwent transperitoneal radical cystectomy with intraperitoneal ileal neobladder. The remaining 48 were submitted to the extraperitoneal technique with extraperitonealization of the neobladder. We compared both methods regarding operating time, intraoperative blood loss, complications and oncological outcome., Results: The incidence of postoperative ileus was significantly lower after the extraperitoneal than after the transperitoneal approach (2/48 vs. 10/47 cases; p = 0.012). However, pelvic lymphoceles were more frequent (6 vs. 0 cases; p = 0.014). The two techniques did not differ with regard to the other major and minor complications, the operating time (mean 377.4 vs. 405.4 min) or the intraoperative blood loss (mean 363 vs. 412 ml). Oncological outcome disclosed no difference between both techniques., Conclusions: The extraperitoneal technique with extraperitonealization of the ileal neobladder is comparable in safety and reliability to the transperitoneal surgical approach and yields good peri- and postoperative results with regard to the parameters we examined. Noteworthy are the significant reduction of postoperative ileus and the higher incidence of lymphoceles. Both may be caused by the separate extraperitoneal regional healing processes.

Background: Sarcosine in urine was recently suggested to be a promising tool in prostate cancer (PCa) diagnostics., Objective: To reevaluate sarcosine as a potential biomarker for early PCa detection and for prediction of tumour aggressiveness., Design, Setting, and Participants: Sarcosine was measured in urine samples from 106 PCa patients and 33 patients with no evidence of malignancy (NEM), confirmed by 8-12 core prostate biopsies, after standardised digital rectal examination, as well as from 12 healthy men and women. The results were related to the clinicopathologic data on prostate volume, tumour stage, Gleason score, and prostate specific antigen (PSA)., Measurements: Sarcosine in urine was determined by gas chromatography-mass spectrometry using a commercial amino acid assay and was normalised to urine creatinine. Nonparametric statistical tests and receiver operating characteristics (ROC) analyses were performed to assess the diagnostic performance., Results and Limitations: The median sarcosine-creatinine ratio in urine was 13% lower in PCa than in NEM patients. Sarcosine values were not associated with tumour stage (pT2 vs pT3) or grade (Gleason score <7 vs > or = 7). ROC analyses proved that the discrimination between PCa and NEM patients was not improved by sarcosine in comparison with total PSA, but it was significantly worse than the percent free PSA. The higher proportion of PCa than NEM patients can be considered a limitation of this study., Conclusions: Sarcosine in urine after rectal digital examination cannot be considered as a suitable marker to differentiate between patients with and without PCa., (Copyright 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

This study aimed to investigate the microRNA (miRNA) profile in prostate carcinoma tissue by microarray analysis and RT-qPCR, to clarify associations of miRNA expression with clinicopathologic data and to evaluate the potential of miRNAs as diagnostic and prognostic markers. Matched tumor and adjacent normal tissues were obtained from 76 radical prostatectomy specimens. Twenty-four tissue pairs were analyzed using human miRNA microarrays for 470 human miRNAs. Differentially expressed miRNAs were validated by TaqMan RT-qPCR using all 76 tissue pairs. The diagnostic potential of miRNAs was calculated by receiver operating characteristics analyses. The prognostic value was assessed in terms of biochemical recurrence using Kaplan-Meier and Cox regression analyses. Fifteen differentially expressed miRNAs were identified with concordant fold-changes by microarray and RT-qPCR analyses. Ten microRNAs (hsa-miR-16, hsa-miR-31, hsa-miR-125b, hsa-miR-145, hsa-miR-149, hsa-miR-181b, hsa-miR-184, hsa-miR-205, hsa-miR-221, hsa-miR-222) were downregulated and 5 miRNAs (hsa-miR-96, hsa-miR-182, hsa-miR-182, hsa-miR-183, hsa-375) were upregulated. Expression of 5 miRNAs correlated with Gleason score or pathological tumor stage. Already 2 microRNAs classified up to 84% of malignant and nonmalignant samples correctly. Expression of hsa-miR-96 was associated with cancer recurrence after radical prostatectomy and that prognostic information was confirmed by an independent tumor sample set from 79 patients. That was shown with hsa-miR-96 and the Gleason score as final variables in the Cox models build in the 2 patient sets investigated. Thus, differential miRNAs in prostate cancer are useful diagnostic and prognostic indicators. This study provides a solid basis for further functional analyses of miRNAs in prostate cancer.

Background: The aim of this questionnaire was to obtain an impression of the practice and applied therapeutic agents in postoperative and adjuvant intravesical therapy of superficial bladder tumours., Patients and Methods: Standardised questionnaires answered by urologists about instillation therapy in 351 patients were analysed., Results: Results showed a discrepancy between the clinical practice and the guidelines in respect of the postoperative instillations and the use of BCG immunotherapy, respectively., Conclusion: It does not seem to be standard practice to treat every patient with one immediate post-operative instillation. Only a minority of high-risk patients received intravesical BCG instillations. Substances mainly used for instillation therapy were mitomycin C and doxorubicin., (Georg Thieme Verlag Stuttgart * New York.)

The specificity of PSA has been enhanced by using molecular forms of PSA and free PSA (fPSA) such as percent free PSA (%fPSA), proPSA, intact PSA or BPHA and / or new serum markers. Most of these promising new serum markers like EPCA2 or ANXA3 still lack confirmation of the outstanding initial results or show only marginally enhanced specificity at high sensitivity levels. PCA3, TMPRSS2-ERG, and other analytes in urine collected after digital rectal examination with application of mild digital pressure have the potential to preferentially detect aggressive PCa and to decrease the number of unnecessary repeat biopsies. The combination of these new urinary markers with new and established serum markers seems to be most promising to further increase specificity of tPSA. Multivariate models, e. g., artificial neural networks (ANN) or logistic regression (LR) based nomograms have recently been performed by incorporating these new markers in several studies. There is generally an advantage to include the new markers and clinical data as additional parameters to PSA and %fPSA within ANN and LR models. Results of these studies and also unexpected pitfalls are discussed in this review.

Channel patency and a cavito-myocardial pressure gradient are prerequisites for one potential mechanism of transmyocardial laser revascularization (TMLR), namely indirect (non-coronary) myocardial perfusion. We assessed the effect of TMLR combined with vascular endothelial growth factor (VEGF) on the myocardial tissue pressure (MTP) in chronic ischemia questioning firstly, whether transmural pressure allows perfusion of laser channels, and secondly, whether additional application of VEGF improves channel patency. One week after creation of an operative left anterior descending artery stenosis (2nd operation), pigs were designated to untreated ischemia (n=7), TMLR (n=8) or TMLR+VEGF-cDNA (2 mg intramyocardially, n=6). MTP and left ventricular pressure (LVP) were recorded simultaneously in the endo-, mid-, and epimyocardium before and after stenosis (1st operation), before and after therapy (2nd operation), and 12 weeks later (3rd operation). Myocardial samples were subjected to immunohistochemistry. Endo- and epimyocardial MTP exceeded LVP in all groups throughout the study, whereas midmyocardial MTP was constantly below LVP (P<0.05). Immediately after combined TMLR+VEGF, the endo-MTP decreased from 246.5+/-44.2 to 176.7+/-20.7 mmHg (P=0.043), remaining higher than LVP. After 12 weeks, it increased to 225.6+/-31.8 mmHg (P=0.04), but did not reach baseline values (P=0.04). Histological examination revealed occluded channels with surrounding vascular proliferation in both treatment groups. Additional VEGF-cDNA application in the vicinity of TMLR channels does not improve long-term patency. Direct blood flow from the cavity into the myocardium is impossible due to the high endomyocardial pressure. This limitation might be overcome by implantation of endomyocardial stents.