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Before postchemotherapy retroperitoneal lymph node dissection (pcRPLND), in patients with metastasized germ cell tumors (GCTs), those harboring necrosis (NEC) cannot be distinguished from those who have teratoma (TER), resulting in relevant overtreatment, whereas microRNA-371a-3p may be predictive for viable GCT. The purpose of this study was to explore messenger RNA (mRNA) and proteins to distinguish TER from NEC in pcRPLND tissue.The discovery cohort consisted in total of 48 patients, including 16 each with TER, viable GCT, and NEC. Representative areas were microdissected. A NanoString panel and proteomics were used to analyze 770 genes and5000 proteins. The most significantly and differentially expressed combination of both parameters, mRNA and its associated protein, between TER and NEC was validated using immunohistochemistry (IHC) in an independent validation cohort comprising 66 patients who were not part of the discovery cohort.The authors observed that anterior gradient protein 2 homolog (AGR2) and keratin, type I cytoskeletal 19 (KRT19) were significantly differentially expressed in TER versus NEC in mRNA and protein analyses (proteomics). The technical validation using IHC was successful in the same patients. These proteins were further validated by IHC in the independent patient cohort and exhibited significantly higher levels in TER versus NEC (p .0001; area under the curve, 1.0; sensitivity and specificity, 100% each).The current study demonstrated that KRT19 and AGR2 mRNA and protein are overexpressed in TER versus NEC in pcRPLND tissue and might serve as a future diagnostic target to detect TER, for instance, by functional imaging, to avoid overtreatment.The proteins and the corresponding genes called AGR2 and KRT19 can differentiate between teratoma and necrosis in remaining tumor masses after chemotherapy in patients who have metastasized testicular cancer. This may be a way to improve presurgical diagnostics and to reduce the current overtreatment of patients with necrosis only, who could be treated sufficiently by surveillance.

OBJECTIVE To assess the mid-term efficacy and safety of anterior urethroplasty using an autologous tissue-engineered oral mucosa graft (MukoCell® ). METHODS The data of 77 patients with anterior urethral strictures undergoing treatment with MukoCell® at a tertiary center from June 2016 to May 2019 were analyzed. Patients' characteristics, pre- and postoperative diagnostics, perioperative complications, and follow-up data were obtained. The overall stricture-free survival, outcomes of the different surgical techniques, stricture localizations, stricture length, early complications of the procedure and risk factors of recurrence were assessed. RESULTS The median follow-up period was 38 months (interquartile range 31-46). The overall recurrence-free rate of anterior urethroplasty using MukoCell® was 68.8%, 24 patients (31.2%) developed a recurrence of the stricture. The stricture recurrences were observed at a median of 7 months (interquartile range 3-13) only in patients with at least one previous surgery or repeated dilatations in their medical history. No oral-urethral adverse events related to the use of MukoCell® were observed, except for a urethrocutaneous fistula (1.3%) requiring reoperation. CONCLUSIONS Anterior one-stage urethroplasty using MukoCell® showed in our hands a mid-term success rate of up to 68.8% without significant adverse events after a median follow-up period of 38 months. This procedure might be an alternative option for long-segment urethral reconstruction.

Objectives To develop and externally validate a risk calculator for prediction of any cancer recurrence in patients with penile squamous cell carcinoma (pSCC) and inguinal lymph node metastases (ILNM), as to date no validated prognostic tool is available for patients with pSCC and ILNM. Patients and methods The development cohort included 234 patients from seven referral centres. The external validation cohort included 273 patients from two additional referral centres. Cox regression identified predictors of any recurrence, which were used to develop a risk calculator. The risk-calculator grouped the development and the validation cohorts according to the individual risk of any recurrence at 24 months (24m-R). Adjuvant treatment effects were tested on overall survival (OS) according to the derived tertiles, within the development and validation cohorts. Results Positive surgical margins, pN3 , and ILNM ratio were associated with higher recurrence rate. The 2-year OS rates were lower for patients with high (>37%) and intermediate (19-37%) compared to low ( 0.1). Conclusion Adjuvant treatment planning is crucial in patients with pSCC with ILNM, where only weak evidence is available. The current tool proved to successfully stratify patients according to their individual risk, potentially allowing better tailoring of adjuvant treatments.

Objectives To evaluate retrospectively the surgical, symptomatic and oncological outcomes of pelvic exenteration surgery (PES) in men with significant intrapelvic complications of locally advanced castration-sensitive (CSPC) and castration-resistant prostate cancer (CRPC). Patients and methods A total of 103 patients with locally advanced progressive and symptomatic CSPC or CRPC underwent PES (radical cystoprostatectomy, n = 71 [68.9%]; radical prostatectomy with continent vesicostomy, n = 9 [8.7%]; total exenteration, n = 23 [22.3%]). All patients underwent local staging via magnetic resonance imaging, cystoscopy and rectoscopy. Systemic staging was carried out with chest, abdominal and pelvic computed tomography scans and bone scans. Peri-operative complications were assessed according to Clavien-Dindo classification. Symptom-free and overall survival were evaluated using the Kaplan-Meier method. Statistical tests were two-tailed with a P value Results After a median (range) follow-up of 36.5 (3-123) months, the symptom-free survival rate at 1 and 3 years was 89.2% (n = 89) and 64.1% (n = 66), respectively. The median symptom-free survival was 27.9 months. A total of 78.6% of the patients were symptom-free during their remaining lifetime. The overall survival rate at 1 and 3 years was 92.2% and 43.7%, respectively, and the median overall survival was 33.6 months. Clavien-Dindo grades 2, 3 and 4 complications developed in 31 (30.6%), 12 (11.6%) and eight patients (8.1%), respectively. Conclusion Pelvic exenteration surgery is technically feasible in well-selected patients, resulting in symptom relief in >90% of patients, covering 80% of their remaining lifetime.

Objectives To identify predictors of poor overall survival (OS) amongst patients with penile squamous cell carcinoma (pSCC) with clinical inguinal lymphadenopathy (cN+), in order to define the best candidates for neoadjuvant chemotherapy (NAC). Patients and methods Using an international, multicentre database of 924 patients with pSCC, we identified 334 men who harboured cN+ with available clinical and follow-up data. Lymph node involvement was defined either by the presence of palpable inguinal node disease or by preoperative computed tomography (CT) assessment. Fluorine-18 fluorodeoxyglucose positron-emission tomography (18 F-FDG-PET)/CT scan was performed based on clinical judgment of the treating physician. Regression-tree analysis generated a risk stratification tool for prediction of 24-month overall mortality (OM). Kaplan-Meier explored the OS benefit related to the use of NAC according to the regression-tree-stratified subgroups. Results Overall, 120 (35.9%), 152 (45.5%), and 62 (18.6%) patients harboured cN1, cN2, and cN3 disease. 18 F-FDG-PET/CT was performed in 48 (14.4%) patients, and 16 (4.8%) had inguinal and pelvic nodal PET detection. The median OS was 107 months, with a 24-month OS of 66%. At regression-tree analysis (area under the curve = 70%), patients with cN3 and cN2 with PET/CT-detected inguinal and pelvic nodal activity had a higher risk of 24-month OM (>50%). NAC was associated with improved 24-month OS rates (54% vs 33%) only in this subgroup of patients (P = 0.002), which was also confirmed after multivariable adjustment (hazard ratio 0.28, 95% confidence interval 0.13-0.62; P = 0.002). Conclusion Patients with pSCC with cN3 or cN2 and inguinal and pelvic 18F-FDG-PET/CT scan detected disease had higher 24-month OM rates according to our regression-tree model. NAC was associated with improved OS only in these subgroups of patients. Our novel decision model may help to stratify cN+ patients, and identify those who most likely will benefit from NAC prior to radical surgical resection.

Background Different bone-modifying agents like bisphosphonates and receptor activator of nuclear factor-kappa B ligand (RANKL)-inhibitors are used as supportive treatment in men with prostate cancer and bone metastases to prevent skeletal-related events (SREs). SREs such as pathologic fractures, spinal cord compression, surgery and radiotherapy to the bone, and hypercalcemia lead to morbidity, a poor performance status, and impaired quality of life. Efficacy and acceptability of the bone-targeted therapy is therefore of high relevance. Until now recommendations in guidelines on which bone-modifying agents should be used are rare and inconsistent. Objectives To assess the effects of bisphosphonates and RANKL-inhibitors as supportive treatment for prostate cancer patients with bone metastases and to generate a clinically meaningful treatment ranking according to their safety and efficacy using network meta-analysis. Search methods We identified studies by electronically searching the bibliographic databases Cochrane Controlled Register of Trials (CENTRAL), MEDLINE, and Embase until 23 March 2020. We searched the Cochrane Library and various trial registries and screened abstracts of conference proceedings and reference lists of identified trials. Selection criteria We included randomized controlled trials comparing different bisphosphonates and RANKL-inihibitors with each other or against no further treatment or placebo for men with prostate cancer and bone metastases. We included men with castration-restrictive and castration-sensitive prostate cancer and conducted subgroup analyses according to this criteria. Data collection and analysis Two review authors independently extracted data and assessed the quality of trials. We defined proportion of participants with pain response and the adverse events renal impairment and osteonecrosis of the jaw (ONJ) as the primary outcomes. Secondary outcomes were SREs in total and each separately (see above), mortality, quality of life, and further adverse events such as grade 3 to 4 adverse events, hypocalcemia, fatigue, diarrhea, and nausea. We conducted network meta-analysis and generated treatment rankings for all outcomes, except quality of life due to insufficient reporting on this outcome. We compiled ranking plots to compare single outcomes of efficacy against outcomes of acceptability of the bone-modifying agents. We assessed the certainty of the evidence for the main outcomes using the GRADE approach. Main results Twenty-five trials fulfilled our inclusion criteria. Twenty-one trials could be considered in the quantitative analysis, of which six bisphosphonates (zoledronic acid, risedronate, pamidronate, alendronate, etidronate, or clodronate) were compared with each other, the RANKL-inhibitor denosumab, or no treatment/placebo. By conducting network meta-analysis we were able to compare all of these reported agents directly and/or indirectly within the network for each outcome. In the abstract only the comparisons of zoledronic acid and denosumab against the main comparator (no treatment/placebo) are described for outcomes that were predefined as most relevant and that also appear in the 'Summary of findings' table. Other results, as well as results of subgroup analyses regarding castration status of participants, are displayed in the Results section of the full text. Treatment with zoledronic acid probably neither reduces nor increases the proportion of participants with pain response when compared to no treatment/placebo (risk ratio (RR) 1.46, 95% confidence interval (CI) 0.93 to 2.32; per 1000 participants 121 more (19 less to 349 more); moderate-certainty evidence; network based on 4 trials including 1013 participants). For this outcome none of the trials reported results for the comparison with denosumab. The adverse event renal impairment probably occurs more often when treated with zoledronic acid compared to treatment/placebo (RR 1.63, 95% CI 1.08 to 2.45; per 1000 participants 78 more (10 more to 180 more); moderate-certainty evidence; network based on 6 trials including 1769 participants). Results for denosumab could not be included for this outcome, since zero events cannot be considered in the network meta-analysis, therefore it does not appear in the ranking. Treatment with denosumab results in increased occurrence of the adverse event ONJ (RR 3.45, 95% CI 1.06 to 11.24; per 1000 participants 30 more (1 more to 125 more); high-certainty evidence; 4 trials, 3006 participants) compared to no treatment/placebo. When comparing zoledronic acid to no treatment/placebo, the confidence intervals include the possibility of benefit or harm, therefore treatment with zoledronic acid probably neither reduces nor increases ONJ (RR 1.88, 95% CI 0.73 to 4.87; per 1000 participants 11 more (3 less to 47 more); moderate-certainty evidence; network based on 4 trials including 3006 participants). Compared to no treatment/placebo, treatment with zoledronic acid (RR 0.84, 95% CI 0.72 to 0.97) and denosumab (RR 0.72, 95% CI 0.54 to 0.96) may result in a reduction of the total number of SREs (per 1000 participants 75 fewer (131 fewer to 14 fewer) and 131 fewer (215 fewer to 19 fewer); both low-certainty evidence; 12 trials, 5240 participants). Treatment with zoledronic acid and denosumab likely neither reduces nor increases mortality when compared to no treatment/placebo (zoledronic acid RR 0.90, 95% CI 0.80 to 1.01; per 1000 participants 48 fewer (97 fewer to 5 more); denosumab RR 0.93, 95% CI 0.77 to 1.11; per 1000 participants 34 fewer (111 fewer to 54 more); both moderate-certainty evidence; 13 trials, 5494 participants). Due to insufficient reporting, no network meta-analysis was possible for the outcome quality of life. One study with 1904 participants comparing zoledronic acid and denosumab showed that more zoledronic acid-treated participants than denosumab-treated participants experienced a greater than or equal to five-point decrease in Functional Assessment of Cancer Therapy-General total scores over a range of 18 months (average relative difference = 6.8%, range -9.4% to 14.6%) or worsening of cancer-related quality of life. Authors' conclusions When considering bone-modifying agents as supportive treatment, one has to balance between efficacy and acceptability. Results suggest that Zoledronic acid likely increases both the proportion of participants with pain response, and the proportion of participants experiencing adverse events However, more trials with head-to-head comparisons including all potential agents are needed to draw the whole picture and proof the results of this analysis.

Objective To investigate non-inferiority of intermittent docetaxel compared to continuous docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC). Patient and methods The investigator initiated randomised phase III study included 187 chemotherapy-naive patients with mCRPC who were allocated to two treatment arms: intermittent docetaxel and continuous docetaxel. Docetaxel was applied in both arms as weekly (35 mg/m2 ) or 3-weekly (75 mg/m2 ). The primary endpoint was 1-year survival, which was tested for non-inferiority (margin δ = 0.125). The secondary endpoints were: overall survival (OS), progression-free survival (PFS), median time to treatment failure (TTF), and toxicity. Results Of 156 eligible patients, 78 were allocated to each arm. The intermittent treatment met the non-inferiority criteria for 1-year survival (two-sided 95% confidence interval, -0.12, 18, P = 0.022), but not for OS, according to the result of a post hoc analysis. The differences between the study arms in PFS and TTF were not significant. The median (range) treatment holiday in the intermittent arm was 110 (13-486) days, or 38% of the overall treatment duration. Safety profiles of both study arms were comparable. The main limitation of this study was that the planned number of patients could not be recruited. Conclusion Intermittent docetaxel chemotherapy was non-inferior to continuous therapy for 1-year survival; non-inferiority in regard to OS was not reached.

Objectives To compare health-related quality of life (HRQOL) between patients with localised prostate cancer in an active surveillance (AS) group and a radical prostatectomy (RP) group, as evidence shows that both groups have similar oncological outcomes. Thus, comparative findings on the patients' HRQOL are becoming even more important to allow for informed treatment decision-making. Patients and methods The Hormonal therapy, Active Surveillance, Radiation, Operation, Watchful Waiting (HAROW) study is a prospective, observational study designed to collect data for different treatment options for newly diagnosed patients with localised prostate cancer under real-life conditions. At 6-month intervals, clinical data (D'Amico risk categories, Charlson Comorbidity Index) and HRQOL (European Organisation for Research and Treatment of Cancer quality of life questionnaire 30-item core questionnaire) were collected. Data were analysed by longitudinal multilevel analysis for patients with localised prostate cancer under AS and RP. Results Data from 961 patients (556 RP, 405 AS) were considered. The follow-up was 3.5 years (median 2 years). The results reveal significant, but not clinically relevant advantages for patients with low-risk prostate cancer managed with AS in contrast to RP concerning global HRQOL as well as role, emotional and social functioning over time, after controlling for age, comorbidities, and partnership status. In some, but not all HRQOL scales, RP patients start with a slightly lower HRQOL and recover up to the level of AS patients within 1-2 years after diagnosis. Conclusion HRQOL is an important aspect in the decision-making and advising process for patients with prostate cancer. In many aspects of HRQOL, AS is associated with more favourable outcomes than RP within the first 1-2 years after diagnosis in our observational design, although the differences were not clinically significant. The result that HRQOL in AS patients is at least as high as in RP patients should be considered when advising patients about the different treatment options for low-risk localised prostate cancer.

Background Gathering health information from Internet websites is increasingly utilized by patients. No data exist about hidradenitis suppurativa (HS)-related online health information. Thus, we aimed to study the quality, popularity, readability, and timeliness of the most frequented websites on HS. Methods Google Trends was used to evaluate the public interest in HS. An Internet search on Google was performed for the terms “hidradenitis suppurativa,” “acne inversa,” and “Verneuil's disease.” Readability scores, HONcode quality certification, Alexa popularity rank, and content were assessed. Results Google search queries on HS have steadily risen in the last 10 years. The website analysis revealed 39 unique websites, which were difficult to read. Ten websites (26%) had HONcode quality certification, and the median (IQR) Alexa popularity rank was 48871 (2333–361275). Thirteen websites (33%) yielded disease-specific photos with a median rating between “quite useful” and “uncertain.” A therapy option with adalimumab was mentioned on 11 websites (28%). Conclusions In addition to an increasing interest, we found a broad variation in the quality, readability, popularity, and timeliness of content on HS-related websites. Improvement of the quality and readability of HS-related websites is desirable to potentially raise disease awareness and contribute to an earlier presentation of patients suffering with undiagnosed HS.

Objective To investigate a cohort of patients undergoing active surveillance (AS) for localized prostate cancer (PCa) with regard to possible differences in discontinuation rates, subsequent therapies, reasons for intervention and pathological findings after deferred surgery after patient stratification into very-low-risk, low-risk and intermediate-/high-risk PCa groups. Patients and Methods The HAROW study was a non-interventional, observational, outcomes research study on the management of localized PCa in the community setting. A total of 468 patients were prospectively enrolled in the HAROW study, with a mean follow-up of 28.5 months. Treating urologists reported clinical variables, information on therapy and clinical course of disease at 6-month intervals. Results Of 468 patients under AS, 244 were stratified into very-low-risk, 142 into low-risk and 82 into intermediate-/high-risk groups. Of these patients, 112 discontinued AS. Discontinuation rates were 25.4% in the very-low-risk, 21.1% in the low-risk and 24.4% in the intermediate-/high-risk groups (P = 0.633). The main reasons for intervention were biopsy upgrade and/or prostate-specific antigen elevation in the very-low- and low-risk groups, and patient preference in the intermediate-/high-risk group (P < 0.05). No significant differences were found regarding subsequent therapies and pathological findings after deferred surgery. Conclusion Our results show no differences in the outcome of risk-stratified patients in the specified risk groups managed with AS, while switching to an invasive treatment on the patient′s request was more frequent in the intermediate-/high-risk group.

To compare the oncological safety of treating patients with penile cancer with conservative techniques developed to preserve function, cosmesis and psychological well-being with more radical ablative strategies. We conducted an extensive review of the literature of penile-preserving and ablative techniques and report on the oncological as well as functional outcomes. There were no randomised studies comparing penile-preserving and ablative techniques. Most studies consisted of retrospective cohorts. The quality of evidence was level 3 at best. Cancer-specific survival is similar in penile-preserving and ablative approaches for low-stage disease. Penile preservation is better for functional and cosmetic outcomes and should be offered as a primary treatment method in men with low-stage penile cancer.

The location of stem cells in the epithelium of the prostatic acinus remains uncertain, as does the cellular origin of prostatic neoplasia. Here, we apply lineage tracing to visualize the clonal progeny of stem cells in benign and malignant human prostates and understand the clonal architecture of this epithelium. Cells deficient for the mitochondrially-encoded enzyme cytochrome c oxidase (CCO) were identified in 27 frozen prostatectomy specimens using dual colour enzyme histochemistry and individual CCO-normal and -deficient cell areas were laser-capture microdissected. PCR-sequencing of the entire mitochondrial genome (mtDNA) of cells from CCO-deficient areas found to share mtDNA mutations not present in adjacent CCO-normal cells, thus proving a clonal origin. Immunohistochemistry was performed to visualize the three cell lineages normally present in the prostatic epithelium. Entire CCO-deficient acini, and part-deficient acini were found. Deficient patches spanned either basal or luminal cells, but sometimes also both epithelial cell types in normal, hyperplastic or atrophic epithelium, and prostatic intraepithelial neoplasia (PIN). Patches comprising both PIN and invasive cancer were observed. Each cell area within a CCO-deficient patch contained an identical mtDNA mutation, defining the patch as a clonal unit. CCO-deficient patches in benign epithelium contained basal, luminal and endocrine cells, demonstrating multilineage differentiation and therefore the presence of a stem cell. Our results demonstrate that the normal, atrophic, hypertrophic and atypical (PIN) epithelium of human prostate contains stem cell-derived clonal units that actively replenish the epithelium during ageing. These deficient areas usually included the basal compartment indicating the basal layer as the location of the stem cell. Importantly, single clonal units comprised both PIN and invasive cancer, supporting PIN as the pre-invasive lesion for prostate cancer.

Little is known about the clonal architecture of human urothelium. It is likely that urothelial stem cells reside within the basal epithelial layer, yet lineage tracing from a single stem cell as a means to show the presence of a urothelial stem cell has never been performed. Here, we identify clonally related cell areas within human bladder mucosa in order to visualize epithelial fields maintained by a single founder/stem cell. Sixteen frozen cystectomy specimens were serially sectioned. Patches of cells deficient for the mitochondrially encoded enzyme cytochrome c oxidase (CCO) were identified using dual-colour enzyme histochemistry. To show that these patches represent clonal proliferations, small CCO-proficient and -deficient areas were individually laser-capture microdissected and the entire mitochondrial genome (mtDNA) in each area was PCR amplified and sequenced to identify mtDNA mutations. Immunohistochemistry was performed for the different cell layers of the urothelium and adjacent mesenchyme. CCO-deficient patches could be observed in normal urothelium of all cystectomy specimens. The two-dimensional length of these negative patches varied from 2-3 cells (about 30 µm) to 4.7 mm. Each cell area within a CCO-deficient patch contained an identical somatic mtDNA mutation, indicating that the patch was a clonal unit. Patches contained all the mature cell differentiation stages present in the urothelium, suggesting the presence of a stem cell. Our results demonstrate that the normal mucosa of human bladder contains stem cell-derived clonal units that actively replenish the urothelium during ageing. The size of the clonal unit attributable to each stem cell was broadly distributed, suggesting replacement of one stem cell clone by another.

Study Type – Diagnostic (case control) Level of Evidence 4 What’s known on the subject? and what does the study add? We know that perineal ultrasound is a well accepted method for women with stress incontinence. We evaluated feasibility of this method for men with stress incontinence after radical prostatectomy. We find differences between continent and incontinent men in amount of fibrosis, mobility of the proximal urethra, bladder neck opening and ability to contract pelvic floor muscles in a sufficient and correct way. OBJECTIVE • To investigate the feasibility and inter-investigator reproducibility of perineal ultrasonography in men with and without post-prostatectomy urinary incontinence (PPI). PATIENTS AND METHODS • This clinical pilot study involved 33 male patients, with a mean (range) age of 67.8 (51–76) years, who underwent radical prostatectomy (RP) ≥1 year ago. • We investigated 21 men with clinically and urodynamically proven grade ≥2 PPI and compared them with 12 men without PPI in objective testing as well as in validated questionnaires. • We used an abdominal 3.5–5 MHz ultrasound probe, which was placed at the perineum between scrotum and anus. With the help of three-/four-dimensional (3D/4D) multislice imaging we obtained good visualization of the bladder neck, the urethra and pelvic floor muscle contraction. • The data from all 33 men was evaluated by two investigators and archived images and videos were also analysed by two independent investigators not present at the actual investigation. RESULTS • Using perineal ultrasonography we were able to visualize hypermobility of the proximal urethra, funnelling of the bladder neck, voluntary pelvic floor contraction, urethral and paraurethral fibrosis, and suture or sling material. • Men with and without PPI differed mainly in the degree of hypermobility of the proximal urethra and opening of the bladder neck. • Inter-investigator agreement was 100% in assessing paraurethral tissue and voluntary muscle contraction and 94% in quantifying mobility of the proximal urethra. • We were able to evaluate the bladder neck opening in 85% of the men. There was 82% agreement between the initial investigators in evaluation of the bladder neck and 76% in quantifying mobility of the proximal urethra using retrospective analysis of stored images. CONCLUSIONS • Two-dimensional and 3D/4D perineal ultrasonography provides more insight into the diagnosis of men with PPI • Perineal ultrasonography can be used further as a visual aid for biofeedback to teach correct muscle contraction of men with stress incontinence after radical prostatectomy.

OBJECTIVE To evaluate preoperative predictive risk factors associated with lymph node metastases (LNM) in a cohort of low-risk prostate cancer (PCA) patients. PATIENTS AND METHODS The charts of 499 patients were retrospectively reviewed to identify prognostic risk factors for the presence of LNM. Pathohistological data and Gleason score of the radical prostatectomy (RP) specimen, number of removed nodes, number of positive lymph nodes, and anatomical distribution of LNM were tabulated and evaluated. A correlation between clinical stage, preoperative serum prostate-specific antigen (PSA), biopsy Gleason score, number of biopsies taken, percentage of positive biopsies and the presence of LNM were calculated. All 499 men underwent retropubic RP and extended pelvic lymphadenectomy (EPLND). RESULTS LNM were identified in 29 (5.8%) patients. A prediction model based on clinical stage, PSA, and biopsy Gleason score had a predictive accuracy of 79.2%. The addition of number of positive biopsies and % positive cores improved its predictive accuracy to 81.5% and 87.8%, respectively. The predicted frequency of LNM by the original nomogram was 7.4% and differed by less than 3% with the actual observation of LNM. The predictive accuracy of the nomogram was 81.5% as compared with 87.8% of the prediction model of this study. CONCLUSIONS The percentage of positive cores involved with PCA is the most reliable predictor of LNM and indicates the need for EPLND. The Briganti nomogram has been validated and a general applicability for predicting the presence of LNM was proven.

What's known on the subject? and What does the study add? The gold standard in the reconstruction of the defect urinary system is still the transplantation of autologous gastrointestinal segments although numerous different types of biomaterials (natural/synthetic) have been investigated as possible replacements. However, the ideal biomaterial is still not identified. In this study, we were able to identify the engineered collagen-based OptiMaix® scaffolds as promising biomaterials for the reconstruction of the urinary tract. OBJECTIVES • To analyse the in vitro cytocompatibility of several engineered collagen-based biomaterials for tissue engineering of the urinary tract. • Tissue-engineered implants for the reconstruction of the urinary tract are of major interest for urological researchers as well as clinicians. Although several materials have been investigated, the ideal replacement has still to be identified. MATERIALS AND METHODS • Several collagen matrices were tested. • Electron microscopy was used to visualize the microstructure of the tested matrices. • Examination of cell attachment and growth of primary porcine urothelial and smooth muscle cells were performed and cell phenotypes were analysed using immunohistochemical stains. • Urea permeability was investigated using Ussing chamber experiments. RESULTS • The best cytocompatibility for both urinary tract-specific cell types was obtained with OptiMaix® (Matricel GmbH, Herzogenrath, Germany) materials. • Cell-specific phenotypes were maintained during culture as shown by immunohistochemical staining. • Furthermore, simultaneous cultivation of both cell types for 7 and 14 days significantly reduced urea permeability. CONCLUSION • These results show the potential of OptiMaix materials in tissue engineering approaches of urinary tract tissues.

The application of stem cells and their use in tissue-engineering approaches is emerging in clinical therapeutic intervention strategies. The use of adult stem cells, either autologous or allogenic, does not raise ethical concerns, in contrast to embryonic stem cells. Mesenchymal stromal cells (MSCs) can be easily obtained from bone marrow or from adipose tissue and further expanded in vitro. Due to their differentiation capacity, MSCs are very attractive for tissue engineering purposes. Furthermore, MSCs secrete a variety of mediators that have beneficial effects on the regenerating tissue. In this review we give an insight into stem cell hierarchy, define the properties of MSCs and summarize recent reports of their administration in urological diseases.

Aims This longitudinal study was performed in order to analyze the incidence of and perioperative risk factors for the development of chronic postsurgical pain (CPSP) in patients after nephrectomy. Methods For baseline data acquisition, valid instruments were used for scoring sociodemographic, psychological, psychosocial, pain, pain treatment, and comorbidity factors: the Mainz Pain Staging System (MPSS) for pain chronicity, the Chronic Pain Grading Questionnaire (CPGQ), the Neuropathic Pain Scale (NPS), the Hospital Anxiety and Depression Scale (HADS), the Short Form 12 (SF-12) for health-related quality of life, the Habitual Well-Being Questionnaire (HWBQ), the Symptom Check List (SCL-8) for detecting psychosomatic dysfunction, and the Weighted Illness Check List (WICL) for evaluation of comorbidities and their impact on activities of daily living. Pain intensities were recorded over the first 6 postoperative days after nephrectomy. A sample of 35 patients was followed up for 3 and 6 months. Results Patients with more intense postoperative pain during the first 6 days had significantly higher preoperative anxiety scores. The incidence of CPSP 3 and 6 months after nephrectomy was 28.6% and 8.6%, respectively. Preoperatively increased anxiety scores, reduced physical health-related quality of life (SF-12), multiple comorbid conditions, and increased comorbidity-related disability were significantly associated with the occurrence of CPSP after 3 months. These patients also reported more severe pain during the first week after surgery. Preoperative “current pain intensity” was significantly increased in CPSP patients. Conclusions Our results demonstrate a multifactorial development of CPSP. This process may contribute not only to the occurrence of chronic postsurgical pain but also to the biopsychosocial impairment in these patients as often seen in other chronic pain populations.

Aims To analyze the prevalence and the severity spectrum of pain and its relationships to health-related quality of life and the bio-psycho-social consequences of pain among patients scheduled for radical prostatectomy. Methods Urological inpatients completed an epidemiological pain questionnaire extensively exploring pre-operative acute and chronic pains in 21 body regions. The severity of pain was determined using von Korff’s Pain Grading (CPGQ). Pain chronicity was estimated employing the Mainz Pain Staging System (MPSS). Anxiety and depressive symptoms were identified with the HADS and the Habitual Well-Being Questionnaire (FW-7). Health-related quality of life was measured using the SF-12. Comorbidities and comorbidity-related interferences with daily activities were ascertained with the Weighted Illness Checklist (WICL). Results Eighty of 115 patients (69.6%) reported about pain during the last 3 months pre-operatively. 28.7% of the pain patients had pain related to urological disease. Severe dysfunctional pain was identified by pain Grades 3 and 4 of the CPGQ in 20% and 13.8%, respectively. Advanced pain chronicity characterized by pain Stages II and III of the MPSS was present in 38.8% and 11.3%. Patients with localized prostate cancer without pain complaints had significantly better health-related quality of life and habitual well-being and lower anxiety and depression scores and fewer comorbidities. Patients with cancer-related and non-cancer pain did not differ in pain chronicity, pain severity, pain intensities, anxiety, comorbidities and physical health (SF12-PCS). Conclusions The high prevalence of severe and chronic pain in cancer patients before scheduled radical prostatectomy – combined with considerable disability effects and markedly reduced quality of life necessitate a short routine screening-analysis of the severity spectrum of pain and psychopathology. Patient self-rated pain chronicity staging and psychological distress analysis will allow a disorder severity-guided treatment and the prevention of suffering and additional new chronic post-surgical pain.

The aim of this study was to evaluate the clinical utility of immunohistochemical staining of human testicular germ cell tumours with the monoclonal antibody 43-9F to distinguish embryonal carcinoma (EC) from other malignant germ cell components in order to facilitate pathohistological assessment of prognostic risk factors for metastatic disease in clinical stage I NSGCT. Archival, formalin-fixed, paraffin-embedded tissue blocks of 24 classical seminomas, 7 spermatocytic seminomas, and 20 non-seminomatous germ cell tumours were stained for 43-9F, AFP, hCG and PLAP expression. Immunohistochemical expression was graded using a semi-quantitative scoring system: 1+ = 0-25%, 2+ = 26-50%, 3+ = 51-75% and 4+ = 76-100%. Positive immunohistochemical staining for 43-9F was found in all embryonal carcinomas and yolk sac tumours (YST); staining intensity was not statistically different between the two tumours (3.8 +/- 1.2 vs. 3.1 +/- 0.9). Classical seminomas and seminomatous components of NSGCT stained positive in 13/24 cases (54%); staining intensity was weak to moderate (1.1 +/- 0.7) in all but two cases (4+). Spermatocytic seminomas demonstrated weak positive immunostaining in 2/7 cases (29%). Adjacent CIS was found in 33/54 (61.1%) of tumours and 24/33 (72.7%) of CIS cells exhibited a weak to moderate staining intensity (1.4 +/- 0.7). AFP expression was found in 93% of YST and in only 10% of EC; however, based on the focal staining pattern, adequate differentiation of YST and EC was not possible. Positive PLAP staining was observed in 75% of EC, 79% of seminomas and in 88% of CIS cells. We did not find 43-9F staining clinically useful to distinguish embryonal carcinoma from other germ cell tumour components such as yolk sac tumour. The detection rate of CIS by 43-9F immunohistochemical staining was low and combination of PLAP staining with light microscopy was even superior. Additionally, our study confirms the link between pre-invasive CIS and embryonal carcinoma and suggests the possible direct development of embryonal carcinoma from CIS.

Department of Surgery, Uniformed Services Uni-versity of the Health Sciences, Bethesda, Mary-land.Presented in part at the 92nd meeting of theAmerican Urological Association, New Orleans,Louisiana, April 12–17, 1997.Supported by a grant from the German ResearchCouncil (A. H.), He 2618/1-1, Deutsche For-schungsgemeinschaft, Bonn, Germany.Address for reprints: Department of Surgery, Uni-formed Services University of the Health Sciences,4301 Jones Bridge Road, Bethesda, MD 20874-4799.Received September 2, 1997; revision receivedJanuary 2, 1998; accepted March 19, 1998.