Psychometric validation of the German version of the EPIC-26 questionnaire for patients with localized and locally advanced prostate cancer.

PURPOSE: For patients with prostate cancer, validated and reliable instruments are essential for measuring patient-reported outcomes. The aim of this study was to validate the German version of the widely established Expanded Prostate Cancer Index Composite with 26 items (EPIC-26). METHODS: A German translation of the original questionnaire was tested in 3094 patients with localized or locally advanced (any T, any N and M0) prostate cancer with treatment intent (including radical prostatectomy, brachytherapy, active surveillance, watchful waiting). They completed the EPIC-26 questionnaire before treatment. A total of 521 of them also completed a questionnaire 12 months afterward. Internal consistency, sensitivity to change, and construct validity were assessed. RESULTS: The internal consistency of all domains was sufficient (Cronbach's alpha between 0.64 and 0.93). Item-to-scale correlation coefficients showed acceptable associations between items and their domain score (all > 0.30), with the lowest scores for "bloody stools" (r = 0.37) and "breast problems" (r = 0.32). Confirmatory and exploratory factor analysis confirmed the five-dimension structure of the EPIC-26 (comparative fit index 0.95). CONCLUSIONS: Psychometric evaluation suggests that the German version of the EPIC-26 is a well-constructed instrument for measuring patient-reported health-related symptoms in patients with prostate cancer.

Analysis of Several Pathways for Efficient Killing of Prostate Cancer Stem Cells: A Central Role of NF-κB RELA.

Prostate cancer is a common cause of death worldwide. Here, we isolated cancer stem cells (CSCs) from four adenocarcinomas of the prostate (Gleason scores from 3 + 3 up to 4 + 5). CSCs were characterized by the expression of the stem cell markers TWIST, the epithelial cell adhesion molecule (EPCAM), the transcription factors SNAI1 (SNAIL) and SNAI2 (SLUG) and cancer markers such as CD44 and prominin-1 (CD133). All investigated CSC populations contained a fraction highly positive for aldehyde dehydrogenase (ALDH) function and displayed robust expressions of programmed cell death 1 (PD-1) ligands. Furthermore, we investigated immunotherapeutic approaches but had no success even with the clinically used PD-1 inhibitor pembrolizumab. In addition, we studied another death-inducing pathway via interferon gamma signaling and detected high-level upregulations of human leukocyte antigen A (HLA-A) and beta 2-microglobulin (B2M) with only moderate killing efficacy. To examine further killing mechanisms in prostate cancer stem cells (PCSCs), we analyzed NF-κB signaling. Surprisingly, two patient-specific populations of PCSCs were found: one with canonical NF-κB signaling and another one with blunted NF-κB activation, which can be efficiently killed by tumor necrosis factor (TNF). Thus, culturing of PCSCs and analysis of respective NF-κB induction potency after surgery might be a powerful tool for optimizing patient-specific treatment options, such as the use of TNF-inducing chemotherapeutics and/or NF-κB inhibitors.

High/low-volume center experience predicts outcome of AMS 800 in male stress incontinence: Results of a large middle European multicenter case series.

AIM: To analyze the influence of implantation volume of artificial sphincters (AMS 800) on outcome in a large central European multicenter cohort study. METHODS: As part of the DOMINO (Debates on Male Incontinence) project, the surgical procedures and outcomes were retrospectively analyzed in a total of 473 patients who received an artificial sphincter (AMS 800) between 2010 and 2012. Clinics that implanted at least 10 AMS 800 per year were defined as high-volume centers. RESULTS: Sixteen centers had a mean rate of 9.54 AMS 800/y of which five clinics were identified as high-volume centers. They implanted significantly more double cuffs (55% vs 12.1%; P < .001), used the perineal approach significantly more often (78% vs 67.7%; P = .003) and chose larger mean cuff sizes (4.63 cm vs 4.42 cm; P = .002). With a mean follow-up of 18 months, the revision rate was significantly higher at low-volume centers (38.5% vs 26.7%; P = .037), urethral erosion being the main reason for revision. Social continence (0-1 pads/24 h) was achieved significantly more often in high-volume centers (45.5% vs 24.2%; P = .002). CONCLUSIONS: Our study showed significantly better continence results and lower revision rates at high-volume centers, confirming earlier results that are still true in this decade. We, therefore, recommend surgery for male incontinence at qualified centers.

The AdVance and AdVanceXP male sling in urinary incontinence: is there a difference?

PURPOSE: To compare the efficacy and perioperative complications of the AdVanceXP with the original AdVance male sling. METHODS: We retrospectively enrolled 109 patients with an AdVance and 185 patients with an AdVanceXP male sling. The baseline characteristics and complication rates were analyzed retrospectively. Functional outcome and quality of life were evaluated prospectively by standardized, validated questionnaires. The Chi2-test for categorical and Mann-Whitney U test for continuous variables were performed to identify heterogeneity between the groups. RESULTS: Regarding operation time, there was no significant difference between the slings (p = 0.146). The complication rates were comparable in both groups except for postoperative urinary retention. This occurred significantly more often in patients with the AdVanceXP (p = 0.042). During follow-up, no differences could be identified regarding ICIQ-SF, PGI or I-QoL or number of pad usage. CONCLUSIONS: The AdVance and AdVanceXP are safe and effective treatment options for male stress urinary incontinence. However, the innovations of the AdVanceXP sling did not demonstrate a superiority over the original AdVance sling regarding functional outcome.

The TiLOOP® Male Sling: Did We Forejudge.

INTRODUCTION: To evaluate the safety and efficacy of the TiLOOP® male sling (pfm medical, Cologne, Germany) used in the treatment for male stress urinary incontinence (SUI). MATERIAL AND METHODS: We retrospectively evaluated a total of 34 patients with a TiLOOP® male sling. Perioperative complication rates were assessed and validated questionnaires were prospectively evaluated to assess quality of life and satisfaction rate. Outcome and complication rates were analysed by using descriptive statistics. Correlation of continence outcome and risk factors was performed with the chi-square test. A p value below 0.05 was considered statistically significant. RESULTS: The majority of patients (70.6%) were diagnosed with mild or moderate male SUI. During surgery, one instance (2.9%) of intraoperative urethral injury was observed. There were no immediate postoperative complications. The mean follow-up time was 44.6 months. An improvement of male SUI was reported by 61.9% of the patients and 38.1% reported no change according the Patient Global Impression of Improvement. The mean perineal pain score was 0.5 according to the international index of pain. CONCLUSIONS: The TiLOOP® is a safe treatment option for male SUI in our cohort with a low complication rate. However, the functional outcome of the TiLOOP® was inferior when compared to the outcome of the AdVance® male sling.

Risk Factors for Failure of Male Slings and Artificial Urinary Sphincters: Results from a Large Middle European Cohort Study.

INTRODUCTION: We analysed the impact of predefined risk factors: age, diabetes, history of pelvic irradiation, prior surgery for stress urinary incontinence (SUI), prior urethral stricture, additional procedure during SUI surgery, duration of incontinence, ASA-classification and cause for incontinence on failure and complications in male SUI surgery. MATERIALS AND METHODS: We retrospectively identified 506 patients with an artificial urinary sphincter (AUS) and 513 patients with a male sling (MS) in a multicenter cohort study. Complication rates were correlated to the risk factors in univariate analysis. Subsequently, a multivariate logistic regression adjusted to the risk factors was performed. A p value <0.05 was considered statistically significant. RESULTS: A history of pelvic irradiation was an independent risk factor for explantation in AUS (p < 0.001) and MS (p = 0.018). Moreover, prior urethral stricture (p = 0.036) and higher ASA-classification (p = 0.039) were positively correlated with explantation in univariate analysis for AUS. Urethral erosion was correlated with prior urethral stricture (p < 0.001) and a history of pelvic irradiation (p < 0.001) in AUS. Furthermore, infection was correlated with additional procedures during SUI surgery in univariate analysis (p = 0.037) in MS. CONCLUSIONS: We first identified the correlation of higher ASA-classification and explantation in AUS. Nevertheless, only a few novel risk factors had a significant influence on the failure of MS or AUS.

Efficacy and safety of the ZSI375 artificial urinary sphincter for male stress urinary incontinence: lessons learned.

PURPOSE: To analyze efficacy and safety for the ZSI375 artificial urinary sphincter in a multicenter case series. METHODS: Thirteen male patients with stress urinary incontinence underwent implantation of a ZSI375 artificial urinary sphincter device between 2010 and 2012 in three international continence reference centers. Perioperative characteristics and postoperative complications were analyzed using the Clavien-Dindo scale. Re-hospitalization and explantation rates, and functional outcome were assessed. Inner-group and between-group differences were analyzed using Wilcoxon, Mann-Whitney U, and Fisher's exact test whenever indicated. Kaplan-Meier analysis was performed to assess device survival. A p value below 0.05 was considered statistically significant. RESULTS: There were no intraoperative complications. Median follow-up was 13.5 months. In this period, four device defects (30.8 %) could be observed, being the main cause for device explantation, followed by device infection (15.4 %), non-resolvable pain (7.7 %), and urethral erosion (7.7 %). There were no Clavien IV or Clavien V complications. Overall explantation rate was 61.5 %. Mean time-to-explantation was 279 ± 308 days. There was no significant influence of previous irradiation and previous invasive incontinence therapy (p = 0.587 and p = 0.685, respectively). Mean daily pad usage decreased from 5.8 ± 1.5 to 2.4 ± 2.1 (p = 0.066). One patient (7.7 %) did not use any pads. Social continence (0-1 pads) was achieved in 15.4 % of the patients. CONCLUSION: This is the most current study that is investigating the outcome after ZSI375 implantation in a multicenter case series. Based on our results, explantation rates after ZSI375 implantation are high and efficacy rates seem lower than previously described. Addressing this high failure rate, the system has undergone a two-step modification in the meantime.

Complications and Short-Term Explantation Rate Following Artificial Urinary Sphincter Implantation: Results from a Large Middle European Multi-Institutional Case Series.

UNLABELLED: Background/Aims/Objectives: To analyze perioperative complication and short-term explantation rates after perineal or penoscrotal single-cuff and double-cuff artificial urinary sphincter (AUS) implantation in a large middle European multi-institutional patient cohort. METHODS: 467 male patients with stress urinary incontinence underwent implantation of a perineal single-cuff (n = 152), penoscrotal single-cuff (n = 99), or perineal double-cuff (n = 216) AUS between 2010 and 2012. Postoperative complications and 6-month explantation rates were assessed. For statistical analysis, Fisher's exact test and Kruskal-Wallis rank sum test, and a multiple logistic regression model were used (p < 0.05). RESULTS: Compared to perineal single-cuff AUS, penoscrotal single-cuff implantation led to significantly increased short-term explantation rates (8.6% (perineal) vs. 19.2% (penoscrotal), p = 0.019). The postoperative infection rate was significantly higher after double-cuff compared to single-cuff implantation (6.0% (single-cuff) vs. 13.9% (double-cuff), p = 0.019). The short-term explantation rate after primary double-cuff placement was 6.5% (p = 0.543 vs. perineal single-cuff). In multivariate analysis, the penoscrotal approach (p = 0.004), intraoperative complications (p = 0.005), postoperative bleeding (p = 0.011), and perioperative infection (p < 0.001) were independent risk factors for short-term explantation. CONCLUSIONS: Providing data from a large contemporary multi-institutional patient cohort from high-volume and low-volume institutions, our results reflect the current standard of care in middle Europe. We indicate that the penoscrotal approach is an independent risk factor for increased short-term explantation rates.

[Urinary incontinence after radical prostatectomy for prostate cancer-data from 17,149 patients from 125 certified centers]. / Harninkontinenz nach radikaler Prostatektomie beim Prostatakarzinom ­ aktuelle Daten von 17.149 Patienten aus 125 zertifizierten Zentren.

BACKGROUND: In addition to erectile dysfunction, urinary incontinence is the most common functional limitation after radical prostatectomy (RPE) for prostate cancer (PCa). The German S3 guideline recommends informing patients about possible effects of the therapy options, including incontinence. However, only little data on continence from routine care in German-speaking countries after RPE are currently available, which makes it difficult to inform patients. OBJECTIVE: The aim of this work is to present data on the frequency and severity of urinary incontinence after RPE from routine care. MATERIALS AND METHODS: Information from the PCO (Prostate Cancer Outcomes) study is used, which was collected between 2016 and 2022 in 125 German Cancer Society (DKG)-certified prostate cancer centers in 17,149 patients using the Expanded Prostate Cancer Index Composite Short Form (EPIC-26). Changes in the "incontinence" score before (T0) and 12 months after RPE (T1) and the proportion of patients who used pads, stratified by age and risk group, are reported. RESULTS: The average score for urinary incontinence (value range: 0-worst possible to 100-best possible) was 93 points at T0 and 73 points 12 months later. At T0, 97% of the patients did not use a pad, compared to 56% at T1. 43% of the patients who did not use a pad before surgery used at least one pad a day 12 months later, while 13% use two or more. The proportion of patients using pads differs by age and risk classification. CONCLUSION: The results provide a comprehensive insight into functional outcome 12 months after RPE and can be taken into account when informing patients.

Is the Standard Artificial Urinary Sphincter AMS 800 Still a Treatment Option for the Irradiated Male Patient Presenting with a Devastated Bladder Outlet?

BACKGROUND: Circular urethral compression with an artificial sphincter allows control of voiding, even in patients with severe stress urinary incontinence, but it heightens the risk of urethral atrophy and erosion. This study of one of the largest populations of patients treated with radiotherapy investigates the additive effect of the post-radiogenic stricture of the membranous urethra/bladder neck on AMS 800 artificial urinary sphincter outcomes. METHODS: In a retrospective multicenter cohort study, we analyzed patients fitted with an AMS 800, comparing those who had received radiotherapy with patients presenting a devastated bladder outlet (stricture of the membranous urethra/bladder neck). We determined the correlation between these groups of patients using both univariate and stepwise adjusted multivariate regression. The revision-free interval was estimated by a Kaplan-Meier plot and compared by applying the log-rank test. A p value below 0.05 was considered statistically significant. RESULTS: Of the 123 irradiated patients we identified, 62 (50.4%) had undergone at least one prior desobstruction for bladder-neck/urethra stenosis. After a mean follow-up of 21 months, the latter tended to achieve social continence less frequently (25.7% vs. 35%; p = 0.08). Revision was required significantly more often for this group (43.1% vs. 26.3%; p = 0.05) due to urethral erosion in 18 of 25 cases. A stenosis recurred in five cases; desobstruction was performed in two cases, leading to erosion in both. Multivariate analysis revealed a significantly higher risk of revision when recurrent stenosis necessitated at least two prior desobstructions (HR 2.8; p = 0.003). CONCLUSIONS: A devastated bladder outlet is associated with a lower proportion of men with social continence and a significantly higher need for revision compared with irradiated patients without a history of urethral stenosis. Alternative surgical procedures should be discussed beforehand, especially in cases of recurrent urethral stenosis.

PSA density lower cutoff value as a tool to exclude pathologic upstaging in initially diagnosed unilateral prostate cancer: impact on hemiablative focal therapy.

PURPOSE: To investigate prostate-specific antigen density as a predictor for pathologic upstaging in patients initially thought to have unilateral prostate cancer. METHODS: We analyzed 438 patients with unilateral prostate cancer in prostate biopsy samples that were treated with radical prostatectomy. Bilateral or extracapsular growth in the final surgical specimens was defined as upstaging. Using Kaplan-Meier curves and a multivariate Cox proportional hazard model, we evaluated the oncologic effect of pathologic upstaging on biochemical recurrence-free survival. Prostate-specific antigen density was evaluated as a diagnostic tool to predict upstaging using ROC-curve analysis. RESULTS: Of the patients, 30.8% had bilateral prostate cancer or extracapsular extension in the surgical specimen. Prostate-specific antigen density was a diagnostic predictor for pathologic upstaging in patients initially thought to have unilateral prostate cancer (AUC 0.62, P < 0.001). Using a lower cutoff value of PSA density <0.056 ng/ml/cm3, upstaging could be excluded in patients with a sensitivity of >98%. CONCLUSIONS: A considerable amount of patients that are initially diagnosed with unilateral prostate cancer on biopsy are underdiagnosed and are upstaged in the radical prostatectomy specimen. In general, AUC of PSA density is too low to use PSA density as diagnostic tool to predict pathologic upstaging in all patients. Nonetheless, PSA density could be used for hemiablative focal therapy decision making using a lower cutoff value of <0.056 ng/ml/cm3.

Women's Perception of Transgastric and Transvaginal Natural Orifice Transluminal Endoscopic Surgery (NOTES) - Impact of Medical Education, Stage of Life and Cross-Cultural Aspects.

Introduction: Despite that NOTES produces at least matchable clinical long-term results when compared to laparoscopy, still a restraint within the medical community and among patients is evident. Consequently, it might be meaningful to evaluate factors of patient's NOTES perception to promote its acceptance. NOTES is still quite novel and questionnaires regarding its perception by the public is still lacking even so in the Middle East. Aim of our survey is to investigate the viewpoint of female healthcare staff on NOTES. Materials and Methods: A total of 350 questionnaires along with written information about Minimally Invasive Surgery and NOTES were distributed among the female staff in a Tertiary-care Hospital in Abu Dhabi, 257 were returned completely anonymously and voluntarily and entered into a database with a response rate of 73%. We surveyed factors like religion, medical background, age as well as history of previous laparoscopy, endoscopy, birth and other aspects that may impact a woman's perception of both transgastric and transvaginal NOTES for cholecystectomy and ovariectomy, respectively. Results: Univariate analyses revealed the majority of Muslim women to be more receptive to NOTES as a choice of surgical technique for cholecystectomy and for ovariectomy, respectively, when compared to Christians and Hindus. However, when compared to Muslims, Christian and Hindu groups had a larger share of medical professions. Women with a medical background would opt significantly less for NOTES. Among younger women, NOTES cholecystectomy was refused due to anxiety concerning future pregnancies and sexual dysfunction. Multinomial logistic regression analysis determined medical background and with independent predictive value for the overall choice of interventional technique (p<0.001). Marital status played a significant role only in the comparison of laparoscopy vs transgastric NOTES when performing cholecystectomy and ovariectomy (p<0.01). Conclusion: In this first study emanating from the Middle East, medical education and partly life stage rather than cross-cultural differences seem to influence NOTES perception in women.

Patients Regret Their Choice of Therapy Significantly Less Frequently after Robot-Assisted Radical Prostatectomy as Opposed to Open Radical Prostatectomy: Patient-Reported Results of the Multicenter Cross-Sectional IMPROVE Study.

Patient's regret (PatR) concerning the choice of therapy represents a crucial endpoint for treatment evaluation after radical prostatectomy (RP) for prostate cancer (PCA). This study aims to compare PatR following robot-assisted (RARP) and open surgical approach (ORP). A survey comprising perioperative-functional criteria was sent to 1000 patients in 20 German centers at a median of 15 months after RP. Surgery-related items were collected from participating centers. To calculate PatR differences between approaches, a multivariate regressive base model (MVBM) was established incorporating surgical approach and demographic, center-specific, and tumor-specific criteria not primarily affected by surgical approach. An extended model (MVEM) was further adjusted by variables potentially affected by surgical approach. PatR was based on five validated questions ranging 0−100 (cutoff >15 defined as critical PatR). The response rate was 75.0%. After exclusion of patients with laparoscopic RP or stage M1b/c, the study cohort comprised 277/365 ORP/RARP patients. ORP/RARP patients had a median PatR of 15/10 (p < 0.001) and 46.2%/28.1% had a PatR >15, respectively (p < 0.001). Based on the MVBM, RARP patients showed PatR >15 relative 46.8% less frequently (p < 0.001). Consensual decision making regarding surgical approach independently reduced PatR. With the MVEM, the independent impact of both surgical approach and of consensual decision making was confirmed. This study involving centers of different care levels showed significantly lower PatR following RARP.

Desmosomal plakophilins in the prostate and prostatic adenocarcinomas: implications for diagnosis and tumor progression.

The plakophilins, members of the armadillo-repeat family, consist of three different proteins (PKP1-3) that are specifically recruited to desmosomal plaques in a highly cell type-specific manner. Using immunofluorescence, immunoelectron microscopy, and immunoblot, we found that all three plakophilins occurred in luminal and basal cells of the pseudostratified prostate epithelium. The analysis of 135 cases of prostatic adenocarcinomas grouped into tumors with low (Gleason score < or = 6), intermediate (Gleason score 7), and high Gleason score (8 < or = Gleason score < or = 10) showed that the expression of PKP1 was reduced or lost in adenocarcinomas with high Gleason scores. The expression of PKP2 was unchanged in all prostatic adenocarcinomas analyzed. In contrast, PKP3 expression was increased in carcinomas with high Gleason scores in comparison with carcinomas with low Gleason scores. In DU 145 cell lines with either overexpression or knockdown of PKP3, both imbalances resulted in fewer desmosomal cell contacts. In addition, overexpression of PKP3 in DU 145 cells led to an augmentation in proliferation rate. Our data imply that both loss of PKP1 and up-regulation of PKP3 expression are biologically important events in prostate cancer and are associated with a more aggressive phenotype.

Prognostic variables for shockwave lithotripsy (SWL) treatment success: no impact of body mass index (BMI) using a third generation lithotripter.

OBJECTIVE: • To investigate the effect of different variables including body mass index (BMI) on therapy outcome in patients with upper urinary tract stones treated with a third generation lithotripter, as BMI has been reported to be an independent predictor for stone-free status after extracorporeal shockwave lithotripsy (SWL) performed with first or second generation lithotripters. PATIENTS AND METHODS: • In all, 172 patients with kidney stones with a mean (range) size of 9.2 (3.0-32.0) mm were included in the study. • In all, 91 patients (52.9%) were treated with a ureteric stent in situ. • For SWL therapy a third generation, electromagnetic lithotripter (Siemens Lithoskop™) was used. Stone-free status was reached, when no more treatable stones were present (no stone or stone < 3 mm). • BMI, stone size and localization, age, gender, treatment parameters and ureteric stent in situ were evaluated for their prognostic relevance on therapy success. RESULTS: • The mean (range) BMI of all patients was 27.8 (19.0-58.6) kg/m(2). • Patients were categorized into two groups: A) patients that were stone free after one treatment; B) patients with residual stones. The mean (sd) BMI was 27.4 (4.6) kg/m(2) and 28.4 (6.1) kg/m(2) for A and B, respectively. • Univariate and multivariate analysis for freedom of stones showed that only stone size (P < 0.01) and presence of a ureteric stent (P = 0.01) were independent prognostic variables. • BMI had no significant influence on therapy outcome (P = 0.51). CONCLUSIONS: • Using a third generation lithotripter, BMI was not an independent predictor of stone-free rate after SWL therapy of kidney stones. • This effect might be attributed to a greater penetration depth of the shockwave energy. Stone size and a ureteric stent in situ were the only variables with prognostic significance.

Treatment decision-making in localized prostate cancer: why patients chose either radical prostatectomy or external beam radiation therapy.

OBJECTIVES: • To evaluate patients' treatment decision-making for localized prostate cancer. • To determine their willingness to participate in a randomized controlled trial (RCT) comparing radical prostatectomy (RP) with external beam radiation therapy (EBRT). PATIENTS AND METHODS: • We investigated 31 patients with localized prostate cancer who had opted for either RP (n= 18) or EBRT (n= 13) as primary therapy. • A semi-structured interview and a short questionnaire were completed a few days after the start of treatment, covering all aspects of treatment decision. RESULTS: • Most patients wanted to decide on their treatment together with their physician and were generally satisfied with the information provided. Internet resources were used more frequently by the RP group (14/18 patients) than by the EBRT group (three of 13 patients, P < 0.01). • Physicians' advice and other patients' experiences were highly influential in the final treatment decisions. • Patients deciding on RP were younger and their personal beliefs were their typical decision criteria (RP, six of 18 patients vs EBRT, none; P= 0.03). By contrast, possible treatment-related side-effects were a major concern for patients choosing EBRT (RP, two of 18, vs EBRT, seven of 14; P= 0.02). • Only two patients (of 31, 6%) would have consented to random assignment to either RP or EBRT, while six (19%) patients were not averse. CONCLUSIONS: • Patients are satisfied with the information provided and with their decision-making process. • Typical modes of reasoning can be found and mainly consist of personal beliefs in patients choosing RP and fear of treatment related side-effects in those choosing EBRT. • According to the sample, the participation rate for a RCT comparing RP to EBRT would not exceed 25% without further efforts.

Small renal cell carcinoma: oncological outcome with tumour size.

OBJECTIVE: The aim of the study was to analyse oncological outcomes of patients with renal cell carcinoma (RCC) up to 4 cm in diameter. MATERIAL AND METHODS: A consecutive series of 396 patients with small RCC was analysed. Tumours were stratified by diameter into three groups: 2 cm (n = 68) for tumours up to 2 cm, 3 cm (n = 172) for tumours between 2.1 and 3.0 cm, and 4 cm (n = 156) for tumours between 3.1 and 4.0 cm in diameter. RESULTS: Tumour stages were distributed into pT1a in 95.6%, 91.9% and 87.0% and into pT3 in 4.4%, 8.1% and 13.0% for the 2 cm, 3 cm and 4 cm groups, respectively. Metastases at the time of diagnosis were found in 2.9% (n = 2), 7.5% (n = 13) and 9.1% (n = 14) of patients in the 2 cm, 3 cm and 4 cm groups, respectively. The tumour-specific survival was 100%, 96.9% and 94.6% at 1 year, 97.5%, 90.3% and 87.5% at 5 years and 97.5%, 87.3% and 84.1% at 10 years for the 2 cm, 3 cm and 4 cm groups, respectively (p < 0.05). CONCLUSIONS: Negative prognostic features as well as worse oncological outcome increase with tumour diameter above 2 cm. These data have important implications when considering active surveillance of small renal tumours.

Nanopore Sequencing Reveals Global Transcriptome Signatures of Mitochondrial and Ribosomal Gene Expressions in Various Human Cancer Stem-like Cell Populations.

Cancer stem cells (CSCs) are crucial mediators of tumor growth, metastasis, therapy resistance, and recurrence in a broad variety of human cancers. Although their biology is increasingly investigated within the distinct types of cancer, direct comparisons of CSCs from different tumor types allowing comprehensive mechanistic insights are rarely assessed. In the present study, we isolated CSCs from endometrioid carcinomas, glioblastoma multiforme as well as adenocarcinomas of lung and prostate and assessed their global transcriptomes using full-length cDNA nanopore sequencing. Despite the expression of common CSC markers, principal component analysis showed a distinct separation of the CSC populations into three clusters independent of the specific type of tumor. However, GO-term and KEGG pathway enrichment analysis revealed upregulated genes related to ribosomal biosynthesis, the mitochondrion, oxidative phosphorylation, and glycolytic pathways, as well as the proteasome, suggesting a great extent of metabolic flexibility in CSCs. Interestingly, the GO term "NF-kB binding" was likewise found to be elevated in all investigated CSC populations. In summary, we here provide evidence for high global transcriptional similarities between CSCs from various tumors, which particularly share upregulated gene expression associated with mitochondrial and ribosomal activity. Our findings may build the basis for identifying novel therapeutic strategies targeting CSCs.

Prognostic factors influencing long-term survival of patients undergoing nephron-sparing surgery for nonmetastatic renal-cell carcinoma (RCC) with imperative indications.

BACKGROUND: We assessed the effect of T stage, Fuhrman's grade, multifocality, bilaterality, positive surgical margins, and synchronism of bilateral tumors on cancer-specific survival of patients with nonmetastatic renal-cell carcinoma (RCC) undergoing nephron-sparing surgery for imperative indications. METHODS: We retrospectively analyzed 168 patients who underwent nephron-sparing surgery for imperative RCC indications between 1974 and 2002. A total of 85 patients had bilateral RCCs; in 27 patients, the tumors were multifocal. Multivariate Cox proportional hazards models were fitted to assess the features associated with cancer-specific survival. RESULTS: The median follow-up was 99 months (range, 2-326 months). Patients were followed until January 2008. A total of 52 patients died of their cancer during follow-up. Multivariate analyses of the total group only revealed Fuhrman's grade 3 (hazard ratio [HR] 2.94) and bilateral occurrence of RCC (HR 1.82) as independent prognostic factors. In a subgroup analysis of patients with bilateral occurrence of RCC, we observed a tendency toward positive surgical margins (HR 2.89, P = 0.08) being another negative prognostic factor. There was no difference in cancer-specific survival between patients with synchronous and metachronous bilateral RCC presence (HR 1.08). CONCLUSIONS: Fuhrman's grade 3 and bilateral occurrence of RCC were the only statistically significant prognostic factors for cancer-specific survival in patients undergoing nephron-sparing surgery for imperative indications for nonmetastatic RCC. The presence of sporadic multifocal tumors and the synchronous occurrence of bilateral tumors have no influence on cancer-specific survival, while positive surgical margins may have an impact in the subset of patients with bilateral RCC.

Enhancer of zeste homolog 2 (EZH2) expression is an independent prognostic factor in renal cell carcinoma.

BACKGROUND: The enhancer of zeste homolog 2 (EZH2) gene exerts oncogene-like activities and its (over)expression has been linked to several human malignancies. Here, we studied a possible association between EZH2 expression and prognosis in patients with renal cell carcinoma (RCC). METHODS: EZH2 protein expression in RCC specimens was analyzed by immunohistochemistry using a tissue microarray (TMA) containing RCC tumor tissue and corresponding normal tissue samples of 520 patients. For immunohistochemical assessment of EZH2 expression, nuclear staining quantity was evaluated using a semiquantitative score. The effect of EZH2 expression on cancer specific survival (CSS) was assessed by univariate and multivariate Cox regression analyses. RESULTS: During follow-up, 147 patients (28%) had died of their disease, median follow-up of patients still alive was 6.0 years (range 0-16.1 years). EZH2 nuclear staining was present in tumor cores of 411 (79%) patients. A multivariate Cox regression analysis revealed that high nuclear EZH2 expression was an independent predictor of poor CSS (> 25-50% vs. 0%: HR 2.72, p = 0.025) in patients suffering from non-metastatic RCC. Apart from high nuclear EZH2 expression, tumor stage and Fuhrman's grading emerged as significant prognostic markers. In metastatic disease, nuclear EZH2 expression and histopathological subtype were independent predictive parameters of poor CSS (EZH2: 1-5%: HR 2.63, p = 0.043, >5-25%: HR 3.35, p = 0.013, >25%-50%: HR 4.92, p = 0.003, all compared to 0%: HR 0.36, p = 0.025, respectively). CONCLUSIONS: This study defines EZH2 as a powerful independent unfavourable prognostic marker of CSS in patients with metastatic and non-metastatic RCC.