The Role of Urine and Washing Cytology in Primary Transurethral Resection of Bladder Tumours.

INTRODUCTION: Urine cytology (UC) is a recommended tool for the diagnosis of urothelial malignancies. Thus far, no specific recommendations regarding the role of washing cytology (WC) have been included in the guidelines. The goal of our study was to analyse the relationship between the histology of transurethrally (transurethral resection of the bladder [TURBT]) resected bladder tumours (BCa) and intraoperative UC or WC findings. MATERIALS AND METHODS: Five hundred consecutive primary TURBT cases conducted between November 2010 and 2015 at our department of the University Hospital Luebeck were retrospectively analysed. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of UC and WC were evaluated to detect BCa. Multivariate logistic regression models were fit to further examine associations between patient- and tumour-related factors and a bladder UC or WC positive for BCa. RESULTS: UC was performed in 297 patients, WC in 294 patients, and both in 261 patients. Sensitivity was 50.7% in UC, 58.1% in WC, and 62.1% for both tests combined. Specificity was 97.8% for UC, 98.0% for WC, and 96.4% for the combined tests. PPV was 98.0% for UC, 98.1% for WC, and 97.2% for combined tests. NPV was 47.8% for UC, 54.5% for WC, and 55.9% for the combined tests. The multivariate analyses revealed no association between positive UC or WC results and subsequent radical cystectomy (UC OR 1.35, 95% CI: 0.3-5.7; WC OR 2.0, 95% CI: 0.4-11.4). Neither UC nor WC was significantly correlated with local recurrence. CONCLUSIONS: Cytologic testing is an important diagnostic tool in BCa detection, showing acceptable sensitivity of around 60% and excellent specificity of over 90%. UC and WC present similar sensitivity. Our results advocate, however, against cytologic testing during primary TURBT, especially with regard to the lack of value in assessing the risk of recurrence. The clinical benefit of taking both types of samples at once is minimal. Furthermore, intraoperative WC collection does not reliably predict subsequent cystectomies.

Global change of surgical and oncological clinical practice in urology during early COVID-19 pandemic.

OBJECTIVES: While the coronavirus disease 2019 (COVID-19) pandemic captures healthcare resources worldwide, data on the impact of prioritization strategies in urology during pandemic are absent. We aimed to quantitatively assess the global change in surgical and oncological clinical practice in the early COVID-19 pandemic. METHODS: In this cross-sectional observational study, we designed a 12-item online survey on the global effects of the COVID-19 pandemic on clinical practice in urology. Demographic survey data, change of clinical practice, current performance of procedures, and current commencement of treatment for 5 conditions in medical urological oncology were evaluated. RESULTS: 235 urologists from 44 countries responded. Out of them, 93% indicated a change of clinical practice due to COVID-19. In a 4-tiered surgery down-escalation scheme, 44% reported to make first cancellations, 23% secondary cancellations, 20% last cancellations and 13% emergency cases only. Oncological surgeries had low cancellation rates (%): transurethral resection of bladder tumor (27%), radical cystectomy (21-24%), nephroureterectomy (21%), radical nephrectomy (18%), and radical orchiectomy (8%). (Neo)adjuvant/palliative treatment is currently not started by more than half of the urologists. COVID-19 high-risk-countries had higher total cancellation rates for non-oncological procedures (78% vs. 68%, p = 0.01) and were performing oncological treatment for metastatic diseases at a lower rate (35% vs. 48%, p = 0.02). CONCLUSION: The COVID-19 pandemic has affected clinical practice of 93% of urologists worldwide. The impact of implementing surgical prioritization protocols with moderate cancellation rates for oncological surgeries and delay or reduction in (neo)adjuvant/palliative treatment will have to be evaluated after the pandemic.

Increased Severe Adverse Outcomes and Decreased Emergency Room Visits for Pyelonephritis: First Report of Collateral Damage during COVID-19 Pandemic in Urology.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic is disrupting urology health-care worldwide. Reduced emergency room visits resulting in adverse outcomes have most recently been reported in pediatrics and cardiology. We aimed to compare patients with emergency room visits for pyelonephritis in 2019 (pre-COVID-19 era) and within the first wave of pandemic in 2020 (COVID-19 era) with regard to the number of visits and severe adverse disease outcomes. METHODS: We performed a retrospective multicentre study comparing characteristics and outcomes of patients with pyelonephritis, excluding patients with hydronephrosis due to stone disease, in 10 urology departments in Germany during a 1-month time frame in March and April in each 2019 and 2020. RESULTS: The number of emergency room visits for pyelonephritis in the COVID-19 era was lower (44 patients, 37.0%) than in the pre-COVID-19 era (76 patients, 63.0%), reduction rate: 42.1% (p = 0.003). Severe adverse disease outcome was more frequent in the COVID-19 era (9/44 patients, 20.5%) than in the pre-COVID-19 era (5/76 patients, 6.6%, p = 0.046). In detail, 7 versus 3 patients needed monitoring (15.9 vs. 3.9%), 2 versus no patients needed intensive-care treatment (4.5 vs. 0%), 2 versus no patients needed drain placement (4.5 vs. 0%), 2 versus no patients had a nephrectomy (4.5 vs. 0%), and 2 versus 1 patient died (4.5 vs. 1.3%). CONCLUSION: This report of collateral damage during CO-VID-19 showed that emergency room visits were decreased, and severe adverse disease outcomes were increased for patients with pyelonephritis in the COVID-19 era. Health authorities should set up information campaign programs actively encouraging patients to utilize emergency room services in case of severe symptoms specifically during the actual second wave of pandemic.

External validation of a postoperative nomogram for the prediction of disease-specific survival in patients with papillary renal cell carcinoma using a large multicenter database.

PURPOSE: Based on data retrieved from a comprehensive multicenter database, we externally validated a published postoperative nomogram for the prediction of disease-specific survival (DSS) in patients with papillary renal cell carcinoma (papRCC). METHODS: A multicenter database containing data of 2325 patients with surgically treated papRCC was used as validation cohort. After exclusion of patients with missing data and patients included in the development cohort, 1372 patients were included in the final analysis. DSS-probabilities according to the nomogram were calculated and compared to actual DSS-probabilities. Subsequently, calibration plots and decision curve analyses were applied. RESULTS: The median follow-up was 38 months (IQR 11.8-80.7). Median DSS was not reached. The c-index of the nomogram was 0.71 (95% CI 0.60-0.83). A sensitivity analysis including only patients operated after 1998 delivered a c-index of 0.84 (95% CI 0.77-0.92). Calibration plots showed slight underestimation of nomogram-predicted DSS in probability ranges below 90%: median nomogram-predicted 5-year DSS in the range below 90% was 55% (IQR 20-80), but the median actual 5-year DSS in the same group was 58% (95% CI 52-65). Decision-curve analysis showed a positive net-benefit for probability ranges between a DSS probability of 5% and 85%. CONCLUSIONS: The nomogram performance was satisfactory for almost all DSS probabilities; hence it can be recommended for application in clinical routine and for counseling of patients with papRCC.

Positive pre-biopsy MRI: are systematic biopsies still useful in addition to targeted biopsies?

PURPOSE: The diagnostic strategy implementing multiparametric magnet resonance tomography (mpMRI) and targeted biopsies (TB) improves the detection and characterization of significant prostate cancer (PCa). We aimed to assess the clinical usefulness of systematic biopsies (SB) in the setting of patients having a pre-biopsy positive MRI. METHODS: A review of the literature was performed in March 2018. All studies investigating the performance of SB in addition to TB (all techniques) were assessed, both in the biopsy-naïve and repeat biopsy setting. RESULTS: Evidence demonstrates that TB improves the detection of index-significant PCa compared with SB alone, in both initial and repeat biopsy settings. However, the combination of both TB and SB improved the overall (around 30%) and significant (around 10%) PCa detection rates as compared with TB alone. Significant differences between both biopsy approaches exist regarding cancer location favoring SB for the far lateral sampling, and TB for the anterior zone. Main current pitfalls of pure TB strategy are the learning curve and experience required for mpMRI reading and biopsy targeting, as well as the precision assessment in TB techniques. CONCLUSION: A pure TB strategy omitting SB leads to the risk of missing up to 15% of significant cancer, due to limitations of mpMRI performance/reading and of precision during lesion targeting. SB remain necessary, in addition to the TB, to obtain the most accurate assessment of the entire prostate gland in this sub-group of patients at risk of significant disease.

Imaging modalities in synchronous oligometastatic prostate cancer.

PURPOSE: Along with a number of other malignancies, the term "oligometastatic" prostate cancer has recently emerged. It represents an attempt to define a subtype of cancer with a limited metastatic load that might perform more favorably than a distinctly disseminated disease, or even one that may be managed in a potentially curative way. Since there is currently a knowledge gap of what imaging modalities should be utilized to classify patients as having this type of tumor, we aimed to shed light on the role of conventional and marker-based imaging in the setting of synchronous oligometastatic prostate cancer as well as summarize the available evidence for its clinical application. METHODS: A literature search on December 15th 2017 was conducted using the Pubmed database. RESULTS: Functional imaging techniques like 68Ga PSMA. 68Ga PSMA PET-CT has currently been shown the best detection rates for the assessment of nodal, bone and visceral metastases, especially for smaller lesions at low PSA levels. CONCLUSIONS: Functional imaging helps detect low-burden disease metastatic patients. However, these imaging modalities are not available in every center and thus clinicians may be prone to prescribe systemic treatment rather than referring patients for cytoreductive treatments. We hope that the ongoing prospective trials will help guide clinicians in making a more personalized management of synchronous metastatic patients.

Websites on Bladder Cancer: an Appropriate Source of Patient Information?

A growing number of patients search for health information online. An early investigation of websites about bladder cancer (BCa) revealed mostly incomplete and particularly inaccurate information. We analyzed the quality, readability, and popularity of the most frequented websites on BCa. An Internet search on www.google.com was performed for the term "bladder cancer." After selecting the most frequented websites for patient information, HONcode quality certification, Alexa popularity rank, and readability scores (according to US grade levels) were investigated. A 36-point checklist was used to assess the content according to the EAU guidelines on BCa, which was categorized into seven topics. The popularity of the 49 websites analyzed was average, with a median Alexa popularity rank of 41,698 (interquartile range [IQR] 7-4,671,246). The readability was rated difficult with 11 years of school education needed to understand the information. Thirteen (27%) websites were HONcode certified. Out of 343 topics (seven EAU guideline topics each on 49 websites), 79% were mentioned on the websites. Of these, 10% contained incorrect information, mostly outdated or biased, and 34% contained incomplete information. Publically provided websites mentioned more topics per website (median [IQR] 7 [5.5-7] vs. 5.5 [3.3-7]; p = 0.022) and showed less incorrect information (median [IQR] 0 [0-1] vs. 1 [0-1]; p = 0.039) than physician-provided websites. Our study revealed mostly correct but partially incomplete information on BCa websites for patients. Physicians and public organizations should strive to keep their website information up-to-date and unbiased to optimize patients' health literacy.

Accordance of Online Health Information on Prostate Cancer with the European Association of Urology Guidelines.

BACKGROUND: The internet is an emerging source of information for prostate cancer (PCa) patients. Since little is known about the quality of information on PCa provided online, we investigated its accordance to the latest European Association of Urology (EAU) guidelines. METHODS: A total of 89 German web pages were included for analysis. A quality model classifying the provider of information and its expertise was introduced. Correctness of provided information was systematically compared to the EAU guidelines. RESULTS: Information was provided by medical experts (41%), media (11%), and pharmaceutical companies (6%). Certificates were found in 23% with a significantly higher rate if provided by medical experts (p = 0.003). The minority of web pages showed information in accordance with the EAU guidelines regarding screening (63%), diagnosis (32%), classification (39%), therapy (36%), complications (8%), and follow-up (27%). Web pages by medical experts as well as websites with any kind of certification showed a significantly higher guideline conformity regarding diagnosis (p = 0.027, p = 0.002), therapy (p = 0.010, p = 0.011), follow-up (p = 0.005, p < 0.001), and availability of references (p = 0.017, p = 0.003). CONCLUSIONS: The present study reveals that online health information on PCa lacks concordance to current guidelines. Certified websites or websites provided by medical experts showed a significantly higher quality and accordance with guidelines.

Acceptance of Adjuvant and Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer in Germany: A Survey of Current Practice.

BACKGROUND: Guidelines support the use of neoadjuvant (NAC) and adjuvant (AC) chemotherapy in muscle-invasive bladder cancer. However, data from North America reported the underutilization of NAC in favor of AC despite the lower level of scientific evidence supporting AC. We aimed to assess current practice patterns of NAC and AC in -Germany. METHODS: A 15-question online survey was developed and sent via email newsletters to members of the -German Association of Urology and of the German Society of Residents in Urology in October 2016 to analyze current practice patterns. RESULTS: The survey yielded 141 individual responses from 61 different German urology departments. Eighty-nine (69.0%) and 119 (93.0%) participants were stated to regularly use NAC and AC respectively. The number of participants who were stated to use NAC and AC regularly was not associated with the type of institution (academic vs. nonacademic), number of hospital beds, and number of cystectomies performed annually. Gemcitabine/cisplatin combination chemotherapy was named as the primarily used NAC regimen by 80 (95%) respondents. The median number of administered cycles was 3 for NAC and 4 for AC. In the case of cisplatin ineligibility, combination chemotherapy with gemcitabine/carboplatin was the most common regimen. Respondents stated that chemotherapy was generally administered by urologists (81% for NAC and 85% for AC). CONCLUSIONS: Our survey of current practice shows a high acceptance rate of NAC in Germany, which was independent of the type of institution. Although the scientific level of evidence for AC is lower, it still seems to be more widely accepted than NAC. NAC and AC were generally administered by urologists.

Mapping the landscape of urology: A new media-based cross-sectional analysis of public versus academic interest.

OBJECTIVES: To quantify public and academic interest in the urological field using a novel new media-based methodology. METHODS: We systematically measured public and academic interest in 56 urological keywords and combined in nine subspecialties. Public interest was quantified as video views on YouTube. Academic interest was quantified as article citations using Microsoft Academic Search. The public-to-academic interest ratio was calculated for a comparison of subspecialties as well as for diseases and treatments. RESULTS: For the selected 56 urological keywords, we found 226 617 591 video views on YouTube and 2 146 287 citations in the academic literature. The public-to-academic interest ratio was highest for the subspecialties robotic urology (ratio 6.3) and andrological urology (ratio 4.6). Prostate cancer was the central urological disease combining both a high public (20% of all video views) and academic interest (26% of all citations, ratio 0.8). Further diseases/treatments of high public interest were premature ejaculation (ratio 54.4), testicular cancer (ratio 11.4), erectile dysfunction (ratio 5.5) and kidney transplant (ratio 3.7). Urological treatments had a higher public-to-academic interest ratio (median ratio 0.25) than diseases (median ratio 0.05; P = 0.029). CONCLUSIONS: A quantification of academic and public interest in the urological field is feasible using a novel new media-based methodology. We found several mismatches in public versus academic interest in urological diseases and treatments, which has implications for research strategies, conference planning and patient information projects. Regular re-assessments of the public and academic interest landscape can contribute to detecting and proving trends in the field of urology.

Testicular Cancer on the Web-an Appropriate Source of Patient Information in Concordance with the European Association of Urology Guidelines?

Despite the continuous growth of the internet, little is known about the quality of online information on testicular cancer, the most common solid malignancy in young men. In our study, we analysed the quality, readability and popularity of the most popular websites on testicular cancer. Therefore, we performed a web search for the term "testicular cancer" using www.google.com . Fifty-one websites were evaluated for HONcode quality certification, Alexa Popularity Rank and readability levels. Furthermore, the websites' content on eight major topics of the current European Association of Urology Guidelines on testicular cancer was assessed. Fourteen (28%) had a HONcode quality certificate and the mean Alexa Popularity Rank of all 51 websites was 54,040 (interquartile range 6648-282,797). Websites were difficult to read requiring 9 years of US school education to properly understand the information. The websites mentioned 80% of the guideline topics on average, revealing "prognosis" (59%) and "follow-up" (57%) as underrepresented subtopics. Furthermore, 12% of all topics were displayed incorrectly, particularly due to wrong information concerning "aetiology" (42%). Sixty percent of the topics were mentioned in an incomplete fashion, with less than half of the websites displaying complete information on "staging" (47%), "diagnostic evaluation" (49%) or "disease management" (45%). In general, online health information concerning testicular cancer is mentioned correctly on most websites. However, improvement regarding readability and completeness of the given information is needed. Nevertheless, highly selected websites on testicular cancer can serve as an appropriate source of patient information.

Feasibility and Efficacy of a Urologic Profession Campaign on Cryptorchidism Using Internet and Social Media.

INTRODUCTION: We performed a professional campaign in Germany intending to establish the urologic profession as a competent and helpful point of contact for patients with cryptorchidism. The aim of this study was to assess the feasibility of this campaign and to quantify the efficacy of using Internet vs. social media. MATERIALS AND METHODS: The strategic design of the campaign comprised a strategy meeting, creation of a landing page, and targeted advertisements on Google in the form of Adwords and on Facebook in the form of sidebar ads and sponsored posts. Outcome measurements were number of impressions, homepage sessions, and downloads of an information brochure. RESULTS: The campaign generated 2,511,923 impressions, 7,369 homepage sessions and 1,086 downloads of information brochures using a total investment budget of 7,500€. Use of Google Adwords was more efficient on outcome measurements than Facebook. A subanalysis of Facebook advertisements showed that sidebar ads and sponsored posts were equally efficient. CONCLUSIONS: New media are an effective platform for a profession campaign. Google Adwords is a more effective and cost-efficient platform than Facebook for a targeted campaign.

Management of Anterior Urethral Strictures in Adults: A Survey of Contemporary Practice in Germany.

INTRODUCTION: Treatment methods of anterior urethral strictures in adults have undergone considerable changes in the recent past. Our goal was to determine national practice patterns among German urologists and to compare results with the results of prior international surveys. METHODS: We conducted a survey on the management of urethral strictures among German urologists. RESULTS: Eight hundred forty-five urologists, representing about 14.6% of German urologists, answered the survey. Most common procedures were direct vision internal urethrotomy (DVIU; 87.2%), blind internal urethrotomy (57.5%), dilatation (56.3%), ventral buccal mucosa graft urethroplasty (31.6%) and excision and primary anastomosis (28.9%). In case of a 3.5-cm bulbar stricture and in the case of a 1-cm bulbar stricture after 2 failed DVIUs, a consecutive urethroplasty was significantly more often favoured compared to transurethral treatment options (44.9 vs. 21.3% and 59.4 vs. 8.3%, both p < 0.001). CONCLUSION: Open urethral reconstruction reveals to be a more common method in practice nowadays. Adherence to recommended treatment algorithms improved in comparison to prior surveys.

Prostate Cancer on the Web-Expedient Tool for Patients' Decision-Making?

Many patients diagnosed with cancer search for health information on the Web. We aimed to assess the quality and reliability of online health information on prostate cancer. Google, Yahoo, and Bing were searched for the term "prostate cancer." After selecting the most frequented websites, quality was measured by DISCERN score, JAMA benchmark criteria, and presence of HONcode certification. Popularity was assessed by Alexa tool, while accessibility, usability, and reliability were investigated by LIDA tool. Readability was analyzed by Flesch-Kincaid Reading Grade Level and Automated Readability Index. All 13 selected websites were rated as being of high quality according to the DISCERN instrument (76.5 ± 2.6 out of 80 points). JAMA benchmark criteria were fulfilled by 87 % of websites, whereas only 37 % were certified by the HONcode. Median Alexa Traffic Rank was 2718 ranging from 7 to 679,038. Websites received 2.3 ± 0.5 daily pageviews per visitor and users spent an average of 2 min 58 s ± 39 sec on the website. Accessibility (92 ± 5 %) and usability (92 ± 3 %) scores were high and reliability (88 ± 8 %) moderate according to the LIDA tool. Flesch-Kincaid Grade Level was 7.9 ± 2.2, and Automated Readability Index was 7.5 ± 2.4, rating the websites as fairly difficult to read. In conclusion, quality, accessibility, and usability of websites on prostate cancer provided a high rating in the current analysis. These findings are encouraging in view of the growing frequency of patients' access of health information online.

R.E.N.A.L. Score Outperforms PADUA Score, C-Index and DAP Score for Outcome Prediction of Nephron Sparing Surgery in a Selected Cohort.

PURPOSE: Several nephrometry scores have been proposed to predict perioperative outcomes in renal surgery. We evaluated which nephrometry score correlates best with the MIC (margin, ischemia and complications) score and quantitative perioperative outcomes in nephron sparing surgery. MATERIALS AND METHODS: Data on 188 patients undergoing nephron sparing surgery were retrospectively investigated for patient, operative and tumor characteristics. Nephrometry scores, including R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, hilar tumor touching the main renal artery or vein and location relative to polar lines), PADUA (preoperative aspects and dimensions used for an anatomical), C-index (concordance index) and DAP (diameter-axial-polar), were measured on preoperative computerized tomography or magnetic resonance imaging and coded continuously and categorically. Parameters pertaining to tumor margin, ischemia and complications were recorded as binary scores and classified as MIC achievement. Operative time, estimated blood loss, warm ischemia time and hospital stay were recorded as quantitative perioperative outcomes. RESULTS: The R.E.N.A.L. score correlated best with MIC and quantitative perioperative outcomes. The continuously coded R.E.N.A.L. score was predictive of MIC on univariate analysis (OR 0.75, 95% CI 0.58-0.97, p = 0.03) and it had the best predictive value on multivariate logistic regression analysis (OR 0.31, 95% CI 0.18-0.82, p = 0.03). The C-index but not the PADUA or the DAP score was predictive of MIC on univariate and multivariate logistic regression analysis. MIC achievement rates were significantly higher for low than for high complexity tumors as assessed by categorically coded R.E.N.A.L. score, C-index and DAP scores. Continuously coded R.E.N.A.L. and PADUA scores positively correlated with operative time, warm ischemia time and hospital stay. The C-index and the DAP score correlated with warm ischemia time. CONCLUSIONS: Of 4 nephrometry scores the R.E.N.A.L. score correlated best with MIC achievement and quantitative perioperative outcomes of nephron sparing surgery.

Integrating Social Media into Urologic Health care: What Can We Learn from Other Disciplines?

Social media (SoMe) have become an integral part in many aspects of personal and professional life. With current uptake rates of 50-70% among urologists, SoMe platforms merit huge potential for dissemination of information and professional exchange among stakeholders in urology. Application of SoMe includes conference conversations via tweet chats, health education via YouTube videos, and Twitter online journal clubs. In addition, a number of urology journals have embraced SoMe to allow rapid dissemination of their content and engagement with their readers. Guidance for the appropriate use of SoMe is provided to urologists by several organizations. Besides urology, other disciplines have adopted SoMe for a variety of areas: continuing professional development, awareness of rare diseases, recruitment of study participants, patient education and support, and publicizing research. Openness to new approaches is the basic prerequisite for a transfer of successful concepts embraced by other specialties, to the field of urology.

Intensified antineoplastic effect by combining an HDAC-inhibitor, an mTOR-inhibitor and low dosed interferon alpha in prostate cancer cells.

A significant proportion of men diagnosed with prostate cancer (PCa) eventually develop metastatic disease, which progresses to castration resistance, despite initial response to androgen deprivation. As anticancer therapy has become increasingly effective, acquired drug resistance has emerged, limiting efficacy. Combination treatment, utilizing different drug classes, exemplifies a possible strategy to foil resistance development. The effects of the triple application of the histone deacetylase (HDAC) inhibitor valproic acid (VPA), the mammalian target of rapamycin inhibitor everolimus and low dosed interferon alpha (IFNα) on PCa cell growth and dissemination capacity were investigated. For that purpose, the human PCa cell lines, PC-3, DU-145 and LNCaP were treated with the combined regimen or separate single agents. Cell growth was investigated by the MTT dye reduction assay. Flow cytometry served to analyse cell cycle progression. Adhesion to vascular endothelium or immobilized collagen, fibronectin and laminin was quantified. Migration and invasion characteristics were determined by the modified Boyden chamber assay. Integrin α and ß subtypes were investigated by flow cytometry, western blotting and RT-PCR. Integrin related signalling, Epidermal Growth Factor Receptor (EGFr), Akt, p70S6kinase and extracellular signal-regulated kinases (ERK)1/2 activation were also assessed. The triple application of VPA, everolimus and low dosed IFNα blocked tumour cell growth and dissemination significantly better than any agent alone. Antitumour effects were associated with pronounced alteration in the cell cycle machinery, intracellular signalling and integrin expression profile. Combining VPA, everolimus and low dosed IFNα might be a promising option to counteract resistance development and improve outcome in PCa patients.

CCL2 promotes integrin-mediated adhesion of prostate cancer cells in vitro.

PURPOSE: Chemokines undergo alterations during neoplasia. However, knowledge about their functional significance in prostate cancer (PCa) progression is still sparse. Since chemokine (C-C motif) ligand 2 (CCL2) is significantly up-regulated in patients with PCa, aim of the current study was to assess whether CCL2 contributes to invasive behavior of prostate cancer cells in vitro. METHODS: The human PCa cell line PC3 was stimulated with CCL2. Cell growth was investigated by MTT dye reduction assay. Cell adhesion was analyzed by measuring attachment to a human endothelial cell (HUVEC) monolayer and immobilized collagen. Cell migration was assessed by a chemotactic assay. Integrin expression on the cell surface was evaluated by Western blot. Blocking studies were performed with anti-integrin α3, anti-integrin α6 and anti-integrin ß4 monoclonal antibodies. RESULTS: PC3 cell growth 72 h after CCL2 exposure was significantly increased, compared to controls. Activation of tumor cells by CCL2 significantly enhanced tumor cell adhesion to HUVEC and immobilized collagen. CCL2, added for 4 or 24 h, elevated α6 and ß4 (4 > 24 h) integrin expression. α3 was enhanced after 4 h, but reduced after 24 h. Blocking either α3, α6 or ß4 led to significant suppression of tumor cell binding to immobilized collagen. CONCLUSIONS: CCL2 stimulates PCa cell adhesion and induces alterations in α3-, α6- and ß4-integrin expression on the cell surface. Blocking these integrins leads to a significant reduction in cell adhesion.

Feasibility, complications and oncologic results of a limited inguinal lymph node dissection in the management of penile cancer.

PURPOSE: In patients with penile cancer (PeCa) and increased risk of inguinal lymphatic dissemination, inguinal lymphadenectomy offers a direct histological staging as the most reliable tool for assessment of the nodal metastasic status and a definitive oncologic treatment simultaneously. However, peri- and/or postoperative mutilating sequalae often occurn. We report on clinical outcome and complications of a limited inguinal lymph node (LN) dissection. MATERIALS AND METHODS: Clinical and histopathological data of all patients with PeCa who underwent limited inguinal lymphadenectomy (LIL) at our institution between 1986 and 2012 were comprehensively analyzed. Perioperative results were presented in relation to one-sided procedures, if appropriate, which were assessed without cross comparison with contralateral LILs. RESULTS: 29 consecutive patients with PeCa aged 60±10.3 years were included in the current study with 57 one-sided LIL performed. Mean operative time for one-sided LIL was 89.0±37.3 minutes with 8.1±3.7 LNs removed. A complication rate of 54.4% (n=31), including 16 minor and 15 major complications was found in a total of 57 procedures with leg oedema being the most prevalent morbidity (15.8%). 4 patients with clinically positive LNs developed inguinal lymphatic recurrence within 9 months after surgery. CONCLUSIONS: Our technique of limited inguinal LN dissection provided an acceptable complication rate without aggravating morbidity. We experienced no recurrences in clinically LN negative patients, so that the approach might be a reasonable option in this scenario. In patients with enlarged LNs, radical inguinal lymphadenectomy still appears to represent the gold standard.