Refluxing versus Non-Refluxing Ureteric Implantation in Continent Cutaneous Urinary Diversion: A Propensity-Scored Comparison regarding Long-Term Renal, Metabolic, and Functional Outcomes of Patients with Ileocecal Pouch.

INTRODUCTION: Studies comparing refluxing versus non-refluxing ureteric implantation in continent cutaneous urinary diversion (CCUD) are scarce and often characterized by heterogeneous study populations. This work therefore aimed at comparing both techniques regarding long-term outcomes in a propensity-scored approach. METHODS: We identified n = 19 patients, totaling n = 38 renal units (RU), who underwent CCUD surgery at our hospital out of a pool of 120 patients. Of these 38 RU, 27 RU were implanted via refluxing ureteric implantation utilizing various procedures due to special intraoperative circumstances (short ureters, damage due to radiation). In terms of preoperative renal function, a comorbidity index (Age-Adjusted Charlson Comorbidity Index [ACCI]), and gender, we compared them to n = 38 patients with a total of 76 RU with non-refluxing ureteric implantation in all RU (1:2 matching). The mean follow-up was 56 (IQR: 23-112) months. RESULTS: Long-term renal function was comparable in CCUD patients receiving refluxing versus non-refluxing ureteric implantation (estimated glomerular filtration rate: 63.11 mL/min vs. 71.7 mL/min, p = 0.22) with an average decline of 17.4 mL/min and 13.69 mL/min during the follow-up period, respectively. Also, the rate of new-onset chronic kidney disease (CKD) (both 15%, p = 1), the need for alkalizing medication, or the number of pyelonephritis episodes did not significantly differ between the groups. In Cox regression analysis, ACCI was the single most predictive parameter for the development of new-onset CKD (HR: 1.71 [1.10-2.66], p = 0.0167). None of the RU in the refluxing group needed revisional surgery concerning the ureterointestinal anastomosis, whereas 7 RU of the non-refluxing group did. CONCLUSIONS: Our study confirms that refluxing ureteric implantation in CCUDs is a valid and safe procedure regarding long-term renal, metabolic and functional outcomes. Our data also suggest that patients should be counseled according to their comorbidities regarding long-term renal function.

Troubleshooting of failed continence mechanisms in the ileocecal pouch: Operative technique and long-term results of the intussuscepted ileal nipple valve.

OBJECTIVES: To provide a detailed step-by-step operative technique, and to report on long-term functional and metabolic outcomes in secondary continence mechanisms in the form of secondary intussuscepted ileal nipple valves in revisional surgery of ileocecal pouches. METHODS: From May 1997 to May 2015, 18 female and 10 male patients suffering from dysfunctional primary continence mechanisms of their ileocecal pouch underwent revisonal surgery to create a secondary ileal nipple valve at our tertiary referral center. The average follow-up period was 65.4 months. RESULTS: After surgery, 24 patients were continent by day and night, and four patients showed minor incontinence with the use of a safety pad. The average frequency of clean intermittent catheterization decreased both during the day and at night. The diameter of the catheters used for clean intermittent catheterization increased significantly. No patient showed stomal stenosis, change of stool habits or metabolic situation in the follow-up period. Furthermore, the creation of the secondary ileal nipple valves did not affect the capacity of the reservoir. In the long-term follow up, two patients required the construction of a third continence mechanism, making for an overall success rate of 92% in the study group. CONCLUSION: To our knowledge, this is the first study of long-term results after the creation of secondary ileal nipple valves. We provide evidence that the creation of a secondary ileal nipple valve is a safe and reliable procedure for continence restoration in ileocecal pouches with excellent functional and metabolic long-term outcomes.

miR-221-5p regulates proliferation and migration in human prostate cancer cells and reduces tumor growth in vivo.

BACKGROUND: Despite latest advances in prostate cancer (PCa) therapy, PCa remains the third-leading cause of cancer-related death in European men. Dysregulation of microRNAs (miRNAs), small non-coding RNA molecules with gene expression regulatory function, has been reported in all types of epithelial and haematological cancers. In particular, miR-221-5p alterations have been reported in PCa. METHODS: miRNA expression data was retrieved from a comprehensive publicly available dataset of 218 PCa patients (GSE21036) and miR-221-5p expression levels were analysed. The functional role of miR-221-5p was characterised in androgen- dependent and androgen- independent PCa cell line models (C4-2 and PC-3M-Pro4 cells) by miR-221-5p overexpression and knock-down experiments. The metastatic potential of highly aggressive PC-3M-Pro4 cells overexpressing miR-221-5p was determined by studying extravasation in a zebrafish model. Finally, the effect of miR-221-5p overexpression on the growth of PC-3M-Pro4luc2 cells in vivo was studied by orthotopic implantation in male Balb/cByJ nude mice and assessment of tumor growth. RESULTS: Analysis of microRNA expression dataset for human primary and metastatic PCa samples and control normal adjacent benign prostate revealed miR-221-5p to be significantly downregulated in PCa compared to normal prostate tissue and in metastasis compared to primary PCa. Our in vitro data suggest that miR-221-5p overexpression reduced PCa cell proliferation and colony formation. Furthermore, miR-221-5p overexpression dramatically reduced migration of PCa cells, which was associated with differential expression of selected EMT markers. The functional changes of miR-221-5p overexpression were reversible by the loss of miR-221-5p levels, indicating that the tumor suppressive effects were specific to miR-221-5p. Additionally, miR-221-5p overexpression significantly reduced PC-3M-Pro4 cell extravasation and metastasis formation in a zebrafish model and decreased tumor burden in an orthotopic mouse model of PCa. CONCLUSIONS: Together these data strongly support a tumor suppressive role of miR-221-5p in the context of PCa and its potential as therapeutic target.

Cognitive Status and Functional Dexterity as Outcome Predictors Following Urinary Diversion: A Combined Retrospective and Prospective Observational Study.

PURPOSE: The study aimed to evaluate the impact of the validated functional dexterity test and the Mini-Mental Status test on subjective functional outcomes, medical care situation, and health-related quality of life (HRQoL) after urinary diversion (UD). PATIENTS AND METHODS: A total of 106 patients (n = 26 ileal conduits, n = 29 neobladders, and n = 51 ileocecal pouches) were included in this combined retrospective (n = 77) and prospective (n = 29) observational study. All patients performed the 2 tests mentioned above and filled out self-designed questionnaires with diversion and HRQoL items. In the prospective cohort, the tests were performed preoperatively and the questionnaires were filled out preoperatively as well as 3 and 6 months after surgery. RESULTS: Reduced dexterity and cognitive skills were significantly associated with increased patient age and subjective constraints in stoma care of ileal conduits, self-catheterization in ileocecal pouches, and continence in neobladders. Overall HRQoL, however, was not affected by dexterity or cognitive measures. CONCLUSIONS: Assessing the cognitive status and functional dexterity of patients undergoing UD might provide a useful objective clinical tool to aid in decision-making regarding the type of UD and postoperative medical care situation. Further prospective data are needed to confirm these findings and further simplify the methods used here.

Serous-lined, stapled pouch wall plication: initial results of a simple and quick novel continence mechanism in troubleshooting secondary to continent cutaneous urinary diversion.

OBJECTIVES: To report a novel and straightforward technique of a secondary continent outlet for continent cutaneous urinary diversion (CCUD) reservoirs without the need for further bowel resection, reducing operating time and length of hospitalization. PATIENTS AND METHODS: From 2015 to 2017, six patients with unreconstructable, incontinent outlets (out of a total pool of 595 patients with CCUD) have undergone the technique described in the present paper at our department. The technique relies on the Mitrofanoff principle, using a stapled full-thickness pouch wall plication, which creates a flap-valve continence mechanism. RESULTS: All patients enjoyed full continence with ease of clean intermittent catheterization (CIC) in the postoperative period and on follow-up to a mean (range) of 12.4 (7-18) months. No major complications were encountered in any patient and the average capacity of the reservoirs was not compromised by the procedure (540 mL preoperatively vs 500 mL in further follow-up). CONCLUSION: In revisional surgery for secondary CCUD incontinence, especially if the patient has already lost a significant amount of bowel or has previously undergone radiation therapy, the technique described here represents a safe and effective alternative to restore continence.

Repair of an Autologous Saphenous Vein Graft Aneurysm Ten Years after Renal Artery Reconstruction during Live Donor Renal Transplantation.

Saphenous vein graft (SVG) aneurysms (SVGA) after renal transplantation represents a rare vascular complication with subsequent challenging multidisciplinary treatment. We present a case of a 30-year-old female who received a live donor kidney transplantation for end-stage renal disease that was caused due to the hemolytic uremic syndrome. Postoperatively, an insufficient graft perfusion due to an arterial kinking was noted and repaired using an autologous SVG interposition. Ten years later, a 3-cm aneurysm of the SVG at the anastomotic site with the common iliac artery was discovered. Multidisciplinary surgical exploration with excision of the aneurysm-carrying vein graft and interposition of a new autologous SVG was successfully carried out with preservation of renal allograft's function. Treatment of SVGA after rental transplantation with a new autologous SVG is challenging but feasible, requiring a multidisciplinary approach in order to guarantee successful rates and to prevent allograft loss.

Long-term results of ileal ureteric replacement: a 25-year single-centre experience.

OBJECTIVE: To report the long-term outcomes of ileal ureteric replacement (IUR) in complex reconstruction of the urinary tract. PATIENTS AND METHODS: From 1991 to 2016, IUR was performed in 157 patients with structural or functional ureteric loss. In 52 patients, bilateral IUR became necessary. Implantation sites where either the native urinary bladder (n = 79) or intestinal reservoirs (n = 78). In the latter group, the technique was used at the time of primary urinary diversion (n = 34), in a secondary approach (n = 29), and in undiversion or conversion procedures (n = 15). Anti-refluxive implantation was performed in 37 patients. In eight patients the ileal ureter was implanted into the cutis as an ileal conduit. All patients were followed prospectively according to a standardised protocol. RESULTS: The mean follow-up was 54.1 months. In 114 patients with dilatation of the upper urinary tract before surgery a significant improvement of the dilatation was confirmed in 98 patients. Serum creatinine levels decreased or remained stable in 147 of the 157 patients. Reflux was present in all cases without and in six cases with an anti-reflux mechanism. In six patients, operative revision became necessary because of severe metabolic acidosis, mucus obstruction or stenosis of the ileal ureter. CONCLUSIONS: To our knowledge, this is the world's largest single-centre series of IUR reported to date. Long-term follow-up confirms that this approach is a safe and reliable solution, even under complex conditions. Anti-refluxive implantation is recommended for intestinal reservoirs, whereas reflux prevention seems to be of minor importance when the native bladder is chosen as the site of implantation.

Preoperative C-Reactive Protein Values as a Potential Component in Outcome Prediction Models of Metastasized Renal Cell Carcinoma Patients Receiving Cytoreductive Nephrectomy.

PURPOSE: To validate preoperative C-reactive protein (CRP) levels as a prognostic marker for survival in a metastasized renal cell carcinoma (mRCC) patient cohort receiving cytoreductive nephrectomy (CN). PATIENTS AND METHODS: By chart review, 146 mRCC patients receiving CN at our tertiary referral centre from 1997 to 2015 were identified retrospectively. All relevant clinicopathological features including laboratory parameters were collected and correlated to overall survival, progression-free survival and cancer-specific survival (CSS). The mean follow-up was 23 months (range 1-168 months). RESULTS: Besides the already established scoring systems like the MSKCC criteria, an elevated preoperative CRP level (≥0.5 mg/dL) was an independent predictor of CSS in our study group including the chosen postoperative adjuvant therapies (TKI vs. immunotherapy vs. others). With regard to morbidity, patients with a good performance status, small tumour size and adequate renal function/haematopoiesis experienced less complication rates, thereby profiting more from CN. CONCLUSIONS: Our data provide indication that preoperative CRP levels should be implemented in nomograms regarding the outcome prediction in mRCC to identify candidates likely to profit from CN.

Diagnosis and Clinical Management of Ruptured Ileocecal Pouches for Continent Cutaneous Urinary Diversion.

BACKGROUND AND OBJECTIVES: The study aimed to report on pouch ruptures in 5 patients with ileocecal reservoirs for continent cutaneous urinary diversion. PATIENTS AND METHODS: Five male patients aged 48-89 were referred to our department between 2000 and 2016 with a ruptured ileocecal pouch 16-175 months postoperatively. RESULTS: With an incidence of 0.95% in our series (5 ruptures in 529 pouch patients out of a pool of 1,182 radical cystectomies) a rupture of the ileocecal pouch is a rare but severe complication. In all the cases, the rupture was supported by the over-distension of the reservoir, while a traumatic self-catheterization was reported in 2 patients. The rupture occurred on the right lateral wall of the ileocecal pouch in 4 out of 5 cases and led to acute abdominal pain and inflammation. Pouchography was performed in all the patients and revealed a leakage in 4 of them. The rupture was verified intraoperatively in 1 patient. Open surgical exploration, drainage and repair were successfully performed in all 5 cases. CONCLUSIONS: Early diagnosis and immediate intervention are mandatory in the cases of pouch rupture to manage this severe complication, which is often related to reduction in patient compliance. Consequently, it is essential to raise awareness of this potentially life-threatening complication in patients with ileocecal pouches.

Long-Term Outcome of Nephron-Sparing Surgery Compared to Radical Nephrectomy for Renal Cell Carcinoma ≥4 cm - A Matched-Pair Single Institution Analysis.

PURPOSE: We investigated the long-term oncological and functional outcome of nephron-sparing surgery/partial nephrectomy (PN) versus radical nephrectomy (RN) for any renal cell carcinoma (RCC) ≥4 cm. PATIENTS AND METHODS: Between 1997 and 2013, we identified 128 patients undergoing PN for RCC ≥4 cm and matched this collective to 128 patients undergoing RN. We then compared overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS) and functional parameters in both groups. The median follow-up time was 58 months (3-210 months). RESULTS: Compared to RN, patients with a PN showed a significantly higher 10-year OS (77.0 vs. 63.0%, p = 0.04), CSS (90.6 vs. 71.7%, p = 0.002) and PFS (82.9 vs. 57.4%, p ≤ 0.001). Renal function preservation was better in the PN group (24 months estimated glomerular filtration rate: 68.2 ml/min for PN vs. 40.6 ml/min for RN, p ≤ 0.01) with significantly less new onset chronic kidney diseases. Total complication rate was comparable, whereas PN procedures showed more Clavien-Dindo grade I + II complications, portraying the technical challenge of PN in larger RCCs. CONCLUSIONS: Whenever feasible, PN should be considered for renal masses ≥4 cm, as this technique shows better long-term results regarding disease-specific survival and renal function preservation in our study group.

Metformin-Derived Growth Inhibition in Renal Cell Carcinoma Depends on miR-21-Mediated PTEN Expression.

PURPOSE: Metformin (MF) acts as a tumour-suppressor in renal cell carcinoma (RCC) by inhibiting the AKT/mTOR pathway via AMPK activation. Here, we explore the influence of miR-21 and its target gene PTEN on MF effects in CAKI-1 and CAKI-2 cells. METHODS: Proliferation assays (MTS) and qRT-PCR after transient transfection with pre- and anti-miR-21 and MF treatment were conducted. AMPK-dependency was assessed via transfection of siAMPK. The expression of PTEN, AKT and miR-21 after transient pre-miR-21 transfection and MF treatment was analysed. RESULTS: We demonstrate that CAKI-1 cells, which were found to be less sensitive towards MF, showed a significant higher miR-21 and lower PTEN expression than CAKI-2. This was confirmed in a primary RCC collective (n = 28): miR-21 and PTEN expression correlated negatively. MF treatment lowered miR-21 AMPK-dependently and increased PTEN expression in the cell lines. Ectopic miR-21 regulation modulated MF sensitivity. Western blot analysis showed that pre-miR-21 transfection and MF treatment regulated PTEN expression with impact on pAKT levels in the cells. CONCLUSIONS: We show that differing MF sensitivity in RCC cells is associated with and mediated through the regulation of miR-21/PTEN expression with an impact on subsequent AKT signalling. This provides imaginable clinical implications regarding MF therapy of RCC patients for the future.

Matched-pair analysis of renal function in the immediate postoperative period: a comparison of living kidney donors versus patients nephrectomized for renal cell cancer.

PURPOSE: Living kidney donation (LKD) involves little risk for the donor and provides excellent functional outcome for transplant recipients. However, contradictory data exist on the incidence and degree of impaired renal function (IRF) in the donor. Only few studies compared the incidence of IRF in donors with that of patients having undergone radical nephrectomy (RN). METHODS: From 1992 to 2012, 94 healthy subjects underwent an open nephrectomy for living kidney donation at the University Medical Center of Würzburg. These patients were compared with matched subjects who had the same surgical procedure for renal cell carcinoma at the Carl-Thiem Hospital Cottbus (1:1 matching using propensity scores). RESULTS: In the LKD-group, no complication ≥ Grade 3 according to the Clavien-Dindo classification occurred. Donors had a preoperative median estimated glomerular filtration rate (eGFR) of 85.1 ml/min which changed to 54.4, 57.0 and 61.0 ml/min (all p < 0.001 in comparison with baseline) on postoperative days 7-10, 365 and 730, respectively. While median eGFR between LKD- and RN-groups was nearly equal (85.1 vs. 85.3 ml/min; p = 0.786), median immediate postoperative eGFR was significantly lower in the LKD-group (54.3 vs. 60 ml/min; p = 0.002). Furthermore, in LKD, the percentage decrease compared with baseline was significantly higher (34.4 vs. 32 %; p = 0.017). CONCLUSIONS: In living kidney donors, median eGFR decreased by 34.4 % immediately after surgery. Compared with matched RN-patients, immediate postoperative IRF is significantly more pronounced. One explanation may be that in kidney tumor patients, compensatory adaptive filtration activity of the contralateral kidney sets in already preoperatively.

The devastated bladder outlet: treatment options.

PURPOSE OF REVIEW: The purpose of this study is to review and discuss recently published studies of therapeutic options in cases with the combination of severe sphincteric damage and recurrent stricture of the bladder neck or anastomosis in patients with postradical prostatectomy. RECENT FINDINGS: Recent focus has been on successful management of recurrent bladder neck contracture with urethral dilatation or endoscopic techniques even in patients with prior history of additional radiation therapy. In addition, some authors include injectable agents in their armamentarium for the treatment of recurrent bladder neck stricture. Failure of all attempts to restore the bladder outlet and urethral patency results in a devastated bladder outlet with persistence of urinary incontinence, sometimes worsened when combined with recurrent obstruction. For this small subgroup of patients with severe damage of the lower urinary tract, treatment options are rare. In the current literature, several case series can be found, but no clinical trials exist to provide an evidence-based approach to this severe disorder. Open reconstructive techniques or urinary diversion with reservoirs made from bowel are necessary in these patients. In recent studies, laparoscopic and robot-assisted approaches have also been described. SUMMARY: In case of a 'nonreconstructible' devastated bladder outlet treatment, options are limited. These devastating conditions require a definitive surgical solution. Bladder neck closure, continent vesicostomy in most cases combined with augmentation or urinary diversion with or without cystectomy are last resort techniques for this problem.

Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is marked by high mortality rate. To date, no robust risk stratification by clinical or molecular prognosticators of cancer-specific survival (CSS) has been established for early stages. Transcriptional profiling of small non-coding RNA gene products (miRNAs) seems promising for prognostic stratification. The expression of miR-21 and miR-126 was analysed in a large cohort of RCC patients; a combined risk score (CRS)-model was constructed based on expression levels of both miRNAs. METHODS: Expression of miR-21 and miR-126 was evaluated by qRT-PCR in tumour and adjacent non-neoplastic tissue in n = 139 clear cell RCC patients. Relation of miR-21 and miR-126 expression with various clinical parameters was assessed. Parameters were analysed by uni- and multivariate COX regression. A factor derived from the z-score resulting from the COX model was determined for both miRs separately and a combined risk score (CRS) was calculated multiplying the relative expression of miR-21 and miR-126 by this factor. The best fitting COX model was selected by relative goodness-of-fit with the Akaike information criterion (AIC). RESULTS: RCC with and without miR-21 up- and miR-126 downregulation differed significantly in synchronous metastatic status and CSS. Upregulation of miR-21 and downregulation of miR-126 were independently prognostic. A combined risk score (CRS) based on the expression of both miRs showed high sensitivity and specificity in predicting CSS and prediction was independent from any other clinico-pathological parameter. Association of CRS with CSS was successfully validated in a testing cohort containing patients with high and low risk for progressive disease. CONCLUSIONS: A combined expression level of miR-21 and miR-126 accurately predicted CSS in two independent RCC cohorts and seems feasible for clinical application in assessing prognosis.

Frozen section analysis of ureteral margins in patients undergoing radical cystectomy for bladder cancer: differential impact of carcinoma in situ in the bladder on reliability and impact on tumour recurrence in the upper urinary tract.

BACKGROUND: Patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) are at risk for upper urinary tract recurrence (UUTR), especially in case of carcinoma in situ (CIS). Data on the impact of CIS in the urinary bladder on ureteral tumour involvement or UUTR are conflicting. We presently evaluate the accuracy of intraoperative frozen section analysis (FSA) of the ureteral margin, the incidence of ureteral tumour involvement and their impact on UUTR in patients undergoing RC for UCB with versus without CIS of the bladder. MATERIAL AND METHODS: Between 2003 and 2007, 243 patients underwent RC in our department. 176 of these for UCB, either without CIS (n = 117, group I) or solitary/concomitant CIS (n = 59, group II). FSA was performed. Patients were followed up for UUTR. RESULTS: Overall, 403 ureteral margins--including re-resections--were analysed (group I, n = 232; group II, n = 171). One patient (0.85%) in group I and 21 patients (35.6%) in group II had tumour involvement of the ureter (p < 0.0001) at the time of RC. The false-negative rate of FSA compared to final histopathology was 0.4% (1/232) for group I and 2.9% (5/171) for group II, respectively. Mean duration of follow-up was 26 months (1-72). In group II, 2 patients (1.1%) had UUTR in the follow-up; both had initially positive and subsequently false-negative FSA. CONCLUSIONS: Tumour involvement of the ureter is found significantly more often in solitary or concomitant CIS of the bladder. Intraoperative ureteral FSA is accurate and should be recommended in these patients. Ureteral tumour involvement predisposes to UUTR especially with initial positive margins mandating careful follow-up.

Ki-67, mini-chromosome maintenance 2 protein (MCM2) and geminin have no independent prognostic relevance for cancer-specific survival in surgically treated squamous cell carcinoma of the penis.

UNLABELLED: What's known on the subject? and what does the study add?: Only little and partly contradictory data are currently published about the prognostic role of immunohistochemically detectable proliferation-associated biomarkers in surgically treated squamous cell carcinoma of the penis (SCCP), and no data are available at present about their usefulness for refining the delineation between different Broders' grading categories (e.g. still G2 or just G3 SCCP?). Moreover, the accuracy of various conventional histopathological parameters for predicting cancer-specific survival (CSS) in surgically treated SCCP has not been systematically evaluated yet. Based on the so far largest study cohort encompassing 158 consecutive patients with surgically treated PSCCs characterised by means of a central histopathological review, our data add the following to the currently available literature: (i) Ki-67, mini-chromosome maintenance 2 protein (MCM2), and geminin indicate a more aggressive behaviour in SCPP but do not represent independent prognostic parameters in the multivariable analysis in terms of CSS, (ii) these three biomarkers are not helpful for refining the delineation between different Broders' grading categories at the immunohistochemical level, and (iii) the conventional histopathological parameters staging, grading, nodal involvement, and lymphovascular invasion are independent prognostic parameters that together achieve a predictive accuracy of 82% for CSS. OBJECTIVE: To assess the role of cell proliferation-associated biomarkers to predict cancer-specific survival (CSS) in patients with surgically treated squamous cell carcinoma of the penis (SCCP). PATIENTS AND METHODS: A multicentre study enrolling 158 consecutive patients with surgically treated SCCP was performed. After conducting a central histopathological review, the staining profiles of Ki-67, mini-chromosome maintenance 2 protein (MCM2) and geminin were evaluated for their correlation with conventional histopathological criteria and their prognostic relevance for predicting CSS in a multivariable Cox proportional hazards regression model (median [interquartile range] follow-up 33 [6-63] months). RESULTS: Staining evaluation showed high interobserver agreement (92-96%). Ki-67 and MCM2 displayed a significant positive correlation with histological tumour grade, lymphovascular invasion (LVI) and nodal status, whereas geminin expression only correlated with tumour grade. The 5-year CSS for the entire study cohort was 62%. Univariable analysis showed a significant prognostic impact of Ki-67 (P = 0.026), MCM2 (P = 0.007), and geminin (P = 0.036). In multivariable analysis, only pT (hazard ratio [HR] 1.67; P = 0.003) and pN stage (HR 2.62; P = 0.015) as well as tumour grade (HR 1.89; P = 0.036) and LVI (HR 2.66; P = 0.028) were identified as independent prognostic parameters for CSS. The accuracy of the Cox model for CSS prediction was 0.820 (95% confidence interval 0.741-0.898). CONCLUSIONS: At present, conventional histopathological criteria remain the most powerful predictors of CSS in surgically treated SCCP. Due to overlapping staining profiles, Ki-67, MCM2 and geminin, either singly or in various combinations, failed to immunohistochemically refine the boundaries between Broders' grading categories. Ki-67, MCM2 and geminin do not represent independent prognostic parameters but reflect a more aggressive behaviour in surgically treated SCCP. Further studies are needed to clarify the currently contradictory predictive role of proliferation-associated biomarkers in terms of predicting nodal involvement in SCCPs.

Is gender becoming relevant in uro-oncological research? A bibliographical analysis.

INTRODUCTION: Gender differences are increasingly recognized as important in numerous diseases and found to be relevant in various cancer entities. While a larger number of manuscripts on gender effects in gastro-intestinal and pulmonary neoplasms have been published, urological malignancies involving men and women alike seem less studied in this regard. The present analysis aimed at describing the role of gender effects in general oncological and uro-oncological research and is the first such bibliometrical analysis. METHODS: The electronic database MEDLINE was searched for relevant medical subject headings from January 1991 to December 2011. Publication types, publishing journal and impact factors were identified. Trends were assessed by linear regression. RESULTS: The numbers of annual publications on all major tumour entities and on urological malignancies increased similarly. While the portion of publications on gender effects was below 1 % for each tumour entity, the annual increase of novel publications on gender effects was significant in most and prominent in pulmonary (1.87, 95 % CI 1.11-2.63; <0.0001) and colorectal neoplasms (2.16, 95 % CI 1.49-2.82; <0.0001). While the annual increase of novel publications on gender effects was significant in bladder cancer (0.33, 95 % CI 0.11-0.54; 0.005), it failed level of significance in renal cell cancer (0.25, 95 % CI -0.19-0.24; 0.82). CONCLUSION: While the overall role of gender effect seems small in general oncological research, it is increasing steadily. In uro-oncological research, such trend is also visible in bladder but not in renal cell cancer. Respective awareness on importance of gender effects should be raised.

Prevalence dependent calibration of a predictive model for nasal carriage of methicillin-resistant Staphylococcus aureus.

BACKGROUND: Published models predicting nasal colonization with Methicillin-resistant Staphylococcus aureus among hospital admissions predominantly focus on separation of carriers from non-carriers and are frequently evaluated using measures of discrimination. In contrast, accurate estimation of carriage probability, which may inform decisions regarding treatment and infection control, is rarely assessed. Furthermore, no published models adjust for MRSA prevalence. METHODS: Using logistic regression, a scoring system (values from 0 to 200) predicting nasal carriage of MRSA was created using a derivation cohort of 3091 individuals admitted to a European tertiary referral center between July 2007 and March 2008. The expected positive predictive value of a rapid diagnostic test (GeneOhm, Becton & Dickinson Co.) was modeled using non-linear regression according to score. Models were validated on a second cohort from the same hospital consisting of 2043 patients admitted between August 2008 and January 2012. Our suggested correction score for prevalence was proportional to the log-transformed odds ratio between cohorts. Calibration before and after correction, i.e. accurate classification into arbitrary strata, was assessed with the Hosmer-Lemeshow-Test. RESULTS: Treating culture as reference, the rapid diagnostic test had positive predictive values of 64.8% and 54.0% in derivation and internal validation corhorts with prevalences of 2.3% and 1.7%, respectively. In addition to low prevalence, low positive predictive values were due to high proportion (> 66%) of mecA-negative Staphylococcus aureus among false positive results. Age, nursing home residence, admission through the medical emergency department, and ICD-10-GM admission diagnoses starting with "A" or "J" were associated with MRSA carriage and were thus included in the scoring system, which showed good calibration in predicting probability of carriage and the rapid diagnostic test's expected positive predictive value. Calibration for both probability of carriage and expected positive predictive value in the internal validation cohort was improved by applying the correction score. CONCLUSIONS: Given a set of patient parameters, the presented models accurately predict a) probability of nasal carriage of MRSA and b) a rapid diagnostic test's expected positive predictive value. While the former can inform decisions regarding empiric antibiotic treatment and infection control, the latter can influence choice of screening method.

Persistent painless hemospermia due to metastatic melanoma of the right seminal vesicle.

BACKGROUND: Metastatic melanoma of the seminal vesicles is a very rare clinical entity and has been reported only once until today in a patient suffering from concomitant HIV infection 12 years ago. CASE PRESENTATION: We report a case of persistent, painless hemospermia in a young Caucasian caused by metastatic malignant melanoma of the right seminal vesicle. The diagnosis was established by magnetic resonance imaging and transrectal ultrasound-guided biopsy. In the subsequent diagnostic workup the primary location of the tumor remained unknown but concomitant pulmonary, hepatic and supraclavicular lymph node metastases have been detected. Despite immediate chemotherapy initiation the patient finally succumbed to his progressive disease six months later. CONCLUSIONS: Malignant melanoma should be considered as a rare differential diagnosis of hemospermia after common causes have been ruled out.

MiR-205 is progressively down-regulated in lymph node metastasis but fails as a prognostic biomarker in high-risk prostate cancer.

The treatment of high-risk prostate cancer (HRPCa) is a tremendous challenge for uro-oncologists. The identification of predictive moleculobiological markers allowing risk assessment of lymph node metastasis and systemic progression is essential in establishing effective treatment. In the current study, we investigate the prognostic potential of miR-205 in HRPCa study and validation cohorts, setting defined clinical endpoints for both. We demonstrate miR-205 to be significantly down-regulated in over 70% of the HRPCa samples analysed and that reconstitution of miR-205 causes inhibition of proliferation and invasiveness in prostate cancer (PCa) cell lines. Additionally, miR-205 is increasingly down-regulated in lymph node metastases compared to the primary tumour indicating that miR-205 plays a role in migration of PCa cells from the original location into extraprostatic tissue. Nevertheless, down-regulation of miR-205 in primary PCa was not correlated to the synchronous presence of metastasis and failed to predict the outcome for HRPCa patients. Moreover, we found a tendency for miR-205 up-regulation to correlate with an adverse outcome of PCa patients suggesting a pivotal role of miR-205 in tumourigenesis. Overall, we showed that miR-205 is involved in the development and metastasis of PCa, but failed to work as a useful clinical biomarker in HRPCa. These findings might have implications for the use of miR-205 as a prognostic or therapeutic target in HRPCa.