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.

The Value and Evaluability of the PCA3 Urine Assay in Prostate Carcinoma is Independent of the Tumor Localization.

INTRODUCTION: The prostate cancer gene 3 (PCA3) test is based on the analysis of tumor cell mRNA in urine. As an exprimated urinary marker, its retrieval is subject to certain physical aspects like palpation pressure and detachment force during the squeezing of cells. Other potential factor of influence may be the distance the cells have to cover until they reach the urethra. Thus, it was investigated whether the localization of the tumors within the prostate with regard to the urethra and the seminal colliculus influences the PCA3 score. METHODS: Prostatectomy specimens of 55 organ-confined prostate cancer patients were processed according to the Stanford protocol. For each prostatectomy specimen, a three-dimensional reconstruction including the surface of the prostate, the tumor areas and the urethra was created. By model simulating, virtual concentric tubes were placed around the urethra and spherical volumes were virtually positioned around the seminal colliculus at diameters of 8, 16 and 32 mm. Depending on localization, tumor volumes may or may not protrude into the tubes or spherical volumes. For each respective diameter, PCA3 levels were compared between the subgroup with and without protrusion of tumor tissue into the tube or spherical ball. RESULTS: For none of the diameters, whether in tubes or spherical balls, were patients without intersection volumes-hence showing peripherally located tumors-found to have lower PCA3 levels. No clinical or histopathological parameter correlated with the PCA3 score. CONCLUSION: The location of the tumor mass in the prostate with respect to the urethra or the seminal colliculus did not to affect the PCA3 score. Hence, the location of the tumor does not limit the validity of the PCA3 score, and even for exclusively peripherall y located tumors, this possible influencing factor did not lead to an artificial modulation of the PCA3 score.

Strategy of robotic surgeons to exert public influence through Twitter.

BACKGROUND: Twitter is gaining growing popularity as a communication platform and potential tool to influence the public in medical matters. The aim here is to examine whether and how robotic surgeons use Twitter more influentially than other urologists. METHODS: Robotic surgeons and other urologists that tweeted at the European urology congress were compared by assessing Twitter Follower/Following Ratio, Retweet Rank and Percentile and their Twitter strategies. RESULTS: Robotic surgeons had a significantly higher Twitter Follower/Following Ratio (2.1, 1.4-2.4) and Retweet Rank percentile (92.1%, 90.5-93%) than other urologists (1.2, 0.8-2.1 and 88.9%, 87.3-91.7%, respectively). Robotic surgeons used original tweet content and links more often than other urologists (69.4% vs 53.8%, and 19.8% vs 12.5%, respectively). CONCLUSIONS: Robotic surgeons had a higher public influence on Twitter than other urologists and posted original tweets and links in tweets and profiles more frequently. This strategy might optimize Twitter use by healthcare professionals in the future. Copyright © 2016 John Wiley & Sons, Ltd.

Minimally invasive versus conventional large-bore percutaneous nephrolithotomy in the treatment of large-sized renal calculi: Surgeon's preference?

OBJECTIVE: The aim of this study was to compare the efficacy and safety of minimally invasive percutaneous nephrolithotomy (MIP) and conventional percutaneous nephrolithotomy (PCNL) in the treatment of patients with large renal stone burden. MIP has proven its efficacy and safety in the management of small renal calculi. However, conventional PCNL is still considered the standard method for treatment of large renal stones in the upper urinary tract. MATERIALS AND METHODS: A search of two longitudinal databases in two tertiary referral centres for complex stone disease identified 133 consecutive patients who were treated by either MIP or PCNL for renal stones 20 mm or larger between January 2009 and August 2012. Clinical data and outcome measures of the two methods were compared by Student's t test, chi-squared test or Fisher's exact test. A p value less than 0.05 was considered statistically significant. RESULTS: Operative time was significantly shorter and hospital stay was significantly longer in conventional PCNL compared to MIP (p = 0.002 and < 0.001, respectively). There were no significant differences in primary stone-free rate or complication rate between the two methods. Only higher graded complications (above Clavien grade II) were significantly more common in conventional PCNL (p = 0.02). CONCLUSION: MIP is equally effective as conventional PCNL in the treatment of large renal calculi. Both methods have a similar complication rate. The shorter operative time in PCNL may be based on the larger diameter and quicker retrieval of large fragments; the longer mean hospital stay may be caused by the handling of the nephrostomy tube. The current data suggest that the choice of the method mainly depends on the surgeon's preference.

Nodal Clearance Rate and Long-Term Efficacy of Individualized Sentinel Node-Based Pelvic Intensity Modulated Radiation Therapy for High-Risk Prostate Cancer.

PURPOSE: To assess the efficacy of individual sentinel node (SN)-guided pelvic intensity modulated radiation therapy (IMRT) by determining nodal clearance rate [(n expected nodal involvement - n observed regional recurrences)/n expected nodal involvement] in comparison with surgically staged patients. METHODS AND MATERIALS: Data on 475 high-risk prostate cancer patients were examined. Sixty-one consecutive patients received pelvic SN-based IMRT (5 × 1.8 Gy/wk to 50.4 Gy [pelvic nodes + individual SN] and an integrated boost with 5 × 2.0 Gy/wk to 70.0 Gy to prostate + [base of] seminal vesicles) and neo-/adjuvant long-term androgen deprivation therapy; 414 patients after SN-pelvic lymph node dissection were used to calculate the expected nodal involvement rate for the radiation therapy sample. Biochemical control and overall survival were estimated for the SN-IMRT patients using the Kaplan-Meier method. The expected frequency of nodal involvement in the radiation therapy group was estimated by imputing frequencies of node-positive patients in the surgical sample to the pattern of Gleason, prostate-specific antigen, and T category in the radiation therapy sample. RESULTS: After a median follow-up of 61 months, 5-year OS after SN-guided IMRT reached 84.4%. Biochemical control according to the Phoenix definition was 73.8%. The nodal clearance rate of SN-IMRT reached 94%. Retrospective follow-up evaluation is the main limitation. CONCLUSIONS: Radiation treatment of pelvic nodes individualized by inclusion of SNs is an effective regional treatment modality in high-risk prostate cancer patients. The pattern of relapse indicates that the SN-based target volume concept correctly covers individual pelvic nodes. Thus, this SN-based approach justifies further evaluation, including current dose-escalation strategies to the prostate in a larger prospective series.

Evaluation of the 'Prostate Interdisciplinary Communication and Mapping Algorithm for Biopsy and Pathology' (PIC-MABP).

INTRODUCTION: Experience from interdisciplinary cooperation revealed the need for a prostate mapping scheme to communicate multiparametric MRI (mpMRI) findings between radiologists, urologists, and pathologists, which should be detailed, yet easy to memorize. For this purpose, the 'Prostate interdisciplinary communication and mapping algorithm for biopsy and pathology' (PIC-MABP) was developed. This study evaluated the accuracy of the PIC-MABP system. METHODS: PIC-MABP was tested and validated in findings of 10 randomly selected patients from routine clinical practise with 18 histologically proven cancer lesions. Patients received an mpMRI of the prostate prior to prostatectomy. After surgery the prostates were prepared as whole-mount step sections. Cancer lesions, which were found suspicious on mpMRI, were assigned to the according PIC-MABP sectors by a radiologist. MpMRI slides were masked and sent to seven urologists from different centres, providing only the PIC-MABP location of each lesion. Urologists marked the accordant regions. Then mpMRI slides were unmasked, and the correctness of each mark was evaluated. RESULTS: One hundred and seventeen of the 126 marks (93%) were correctly assigned. Detection rates differed for lesions >0.5 cc compared with lesions <0.5 cc (p < 0.005): 3/7 (43%) marks were correctly assigned in lesions <0.3 cc, 16/21 (76%) in lesions with 0.3-0.5 cc, and 98/98 (100%) in lesions >0.5 cc. Interobserver agreement was good for lesions >0.5 cc and poor for lesions <0.3 cc (Fleiss Kappa 1 vs. 0.0175). CONCLUSION: PIC-MABP seems to be a reliable system to communicate the location of mpMRI findings >0.5 cc between different disciplines and can be a useful guidance for cognitive mpMRI/TRUS fusion biopsy.

Clearance of Stone Fragments and Stone Dust by Continuous Flow Hydrodynamics in Percutaneous Renal Surgery: An In Vitro Study.

PURPOSE: To investigate the capacity of stone clearance in common percutaneous nephrolithotomy (PCNL) systems achieved solely by hydrodynamic effects in an in vitro setting. METHODS: A watertight cylindrical cast with a caliceal void served as an in vitro model. Various instruments for percutaneous renal surgery working with both continuous flow (fCF) and open Rutner sidearm (fCO) were tested. The model was loaded with standardized artificial stone material (2 mm in diameter) to examine stone removal by the vacuum cleaner effect and with sand (0.1-0.5 mm in diameter) to measure the washout effect caused by irrigation backflow. The association between washout of gravel and irrigation pressure was analyzed using ANOVA. Regression analysis was performed to assess the influence of the instruments' hydrodynamic characteristics-effective cross section of the outflow and irrigation flow volume. RESULTS: Provoking the vacuum cleaner effect removal of stones was only effective in fCF but not in fCO instruments. Depending on irrigation pressure, the volumetric flow rate and effective cross section of the outflow clearance of sand could be observed in various medium- and large-sized fCF and fCO instruments, whereas in small-sized systems, clearance effects were negligible. Regression analysis showed clearance of stone dust strongly associated with an instrument's volumetric flow rate. CONCLUSIONS: This in vitro study demonstrated that the application of medium- and large-sized fCF PCNL systems removes both "insignificant" stones and dust solely by hydrodynamic effects. Further studies have to show if these effects also occur in the in vivo situation.

Utilization of surgical safety checklists by urological surgeons in Germany: a nationwide prospective survey.

OBJECTIVES: We aimed to investigate the contemporary usage rate and habits of the WHO Surgical Safety Checklist (SSC) in German urological departments. METHODS: We designed a 26-item questionnaire that was sent to all urological departments in Germany. The primary aim of this study was to evaluate the usage rate of the SSC. Secondary aims were to compare perioperative characteristics of users vs. non-users of the SSC and to assess circumstances of the SSC application. RESULTS: A total of 213 of 234 (91 %) urological departments were users of the SSC, and 21 (9 %) were non-users. SSC users had more often a standard protocol, took less time and had fewer people involved for checking perioperative patient data compared to non-users. Financial budgeting for the SSC existed in 55 (24 %) departments and for patient safety in 73 (32 %) departments. CONCLUSIONS: The usage rate of the SSC in urological departments in Germany is high despite restricted financial budgeting. Users of the SSC profit by saving time and manpower for checking perioperative patient data.

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.

Risk and timing of biochemical recurrence in pT3aN0/Nx prostate cancer with positive surgical margin - A multicenter study.

BACKGROUND AND PURPOSE: Positive surgical margins (PSM) after radical prostatectomy have been shown to be associated with impaired outcome. In pT3pN0 patients with PSM either immediate radiotherapy or clinical and biological monitoring followed by salvage radiotherapy is recommended by the latest guidelines of the European Association of Urology. MATERIALS AND METHODS: A retrospective, multicenter study of eight urological centers was conducted on 536 prostatectomy patients with pT3aN0/NxR1 tumors and no neoadjuvant/adjuvant therapy. A pathological re-review of all prostate specimens was performed. Association of clinical and pathological features with biochemical recurrence (BCR) was analyzed using univariate and multivariate analysis. RESULTS: With 48months median follow-up, BCR occurred in 39.7%. Preoperative PSA value, performance of pelvic lymph node dissection and Gleason score were significantly associated with BCR. In multivariate analysis, Gleason score was the only independent prognostic factor (p<0.001) for BCR. Five-year BCR-free survival rates were 74%, 70%, 38%, and 51% with Gleason score 6, 3+4=7a, 4+3=7b, and 8-10, respectively. CONCLUSIONS: In pT3aN0/NxR1 patients with no adjuvant/neoadjuvant treatment, Gleason Score permits independent prediction of the risk for BCR. These findings could help to estimate and discuss the individual risk for BCR with our patients on an individual basis.

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

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.

The vacuum cleaner effect in minimally invasive percutaneous nephrolitholapaxy.

INTRODUCTION: Percutaneous stone removal increasingly plays an important role among the different approaches of interventional stone therapy, particularly since the development of miniaturized instruments is resulting in lower morbidity for the patients. One major drawback of smaller instruments is the increased difficulty of stone retrieval after disintegration due to the reduced tract diameter. This results in longer operation time and the need of additional tools such as disposable retrieval baskets. One of the key factors in the development of minimally invasive percutaneous nephrolitholapaxy (MIP) was the design of an Amplatz sheath which provides a built-in vacuum cleaner effect for stone retrieval. METHODS: A series of flow analyses with the gauges and shapes of the most commonly used nephroscopes and sheaths in percutaneous nephrolitholapaxy was performed by computational fluid dynamics. Flow velocity and direction in front of the nephroscope were computed and visualized by the software. RESULTS: In our study, the vacuum cleaner effect developed exclusively when a round-shaped nephroscope was used (Nagele Miniature Nephroscope System, Karl Storz GmbH & Co. KG) and depended on the relation between nephroscope diameter and inner sheath diameter. The strongest effect was observed with a 12 F nephroscope and an inner sheath diameter of 15 F. It did not develop when an oval- or crescent-shaped nephroscope was used. In front of the distal end of the round-shaped nephroscope, a slipstream develops, induced by the excursive change of width of the fluid flow on the outlet of the flushing canal. This allows the adhesion of a stone fragment in the eddy while the fluid flow is circulating around the stone. CONCLUSION: This study illustrates and explains the vacuum cleaner effect which has been detected in the development of the Nagele Miniature Nephroscope System used in MIP. It combines the reduced morbidity of smaller kidney puncture diameters with the benefit of quick and complete stone removal.

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.

PCA3 and PSA gene activity correlates with the true tumor cell burden in prostate cancer lymph node metastases.

BACKGROUND: Extent of pelvic lymph node (LN) dissemination is a critical prognostic feature for patients with prostate cancer (PCa) maintaining extended pelvic lymphadenectomy (LAD) as the gold standard for LN-staging. Unfortunately, conventional histopathological assessment may miss micrometastasis and recently presented immunocytochemical approach of the single cell analysis is still intricate. OBJECTIVE: To comparatively assess the potential of Prostate cancer gene 3 (PCA3) and prostate specific antigene (PSA) to perform as markers for tumor cell load. METHODS: Patients with high risk PCa for LN metastasis undergoing either a sentinel LN-guided staging LAD or retropubic radical prostatectomy with sentinel-guided pelvic LN dissection were included. LNs were investigated by routine histopathology. Tumor cell load was quantified by %immunocytochemistry. immunocytochemical single cell analysis. Gene activity was determined by qRT-PCR. RESULTS: Twenty four out of 226 LNs were positive in routine histopathology and 51 in single cell analysis. PSA mRNA level correlated with tumor cell density in patients with a positive immunocytochemistry. Gene activity of PCA3 was upregulated in metastatic LNs and correlated with tumor cell density in patients with tumor-invaded LNs as detected by immunocytochemistry. CONCLUSIONS: PCA3 gene expression discriminates LN metastasis and might outperform PSA gene activity in reflecting tumor cell burden in pelvic LNs of PCa patients.

Significance of apoptotic and non-apoptotic disseminated tumor cells in the bone marrow of patients with clinically localized prostate cancer.

BACKGROUND: Disseminated tumor cells (DTC) can be detected in a high proportion of patients with localized solid malignancies. In prostate cancer (PC), determination of DTCs is critically discussed as there are conflicting results on their prognostic value. The aim of the present study was to evaluate the presence and prognostic role of DTCs in PC patients with a high risk of disease recurrence. METHODS: 248 patients with clinically localized PC undergoing radical prostatectomy with features of increased risk of recurrence (PSA ≥10 ng/ml or Gleason score ≥ 4 + 3 = 7 or pT ≥3) were included. All patients underwent intraoperative bone marrow (BM) aspiration biopsy. BM cells were evaluated by immunocytochemistry for cytokeratines and the apoptosis marker caspase-cleaved cytokeratin 18 (M30). Results of immunocytochemistry were correlated with clinical and pathological parameters and clinical outcome of the patients. RESULTS: Of 248 patients, 47 (19.0%) had evidence of DTCs at time of radical prostatectomy. In 17 of these 47 patients (36.2%), DTCs expressed the apoptosis marker M30. We observed no correlation between the presence of DTCs and tumor stage, nodal stage, prostate-specific antigen, or Gleason score. After a median-follow-up of 58 months (23-76), no differences in rates of biochemical recurrence, development of metastases and cancer-specific death were observed between patients with and without DTCs while apoptosis markers had no role. CONCLUSIONS: In a single-centre cohort of patients with increased risk for disease recurrence, the presence of DTCs at the time of prostatectomy does not influence clinical outcome. For the first time in patients with PC, DTCs were evaluated for immunocytological features indicating apoptosis. Due to conflicting results of studies on DTCs, BM biopsies at time of radical prostatectomy cannot be recommended as a standard procedure in patients with clinically localized PC.

Flow matters 2: How to improve irrigation flow in small-calibre percutaneous procedures-the purging effect.

INTRODUCTION: Aim of this study was to investigate whether the combination of high-pressure irrigation inflow combined with simultaneous sensor-controlled suction could improve irrigation turnover without leading to high peak intrarenal pressure in small-calibre percutaneous instruments (SCPI). M + M: A MIP XS sheath (9.5 Fr. outer diameter and 8.5 Fr. inner diameter) and a 7.5-Fr. nephroscope (3-Fr. irrigation channel; MIP XS by Nagele, Karl Storz, Tuttlingen, Germany) was inserted into the collecting system of a non-perfused cadaveric porcine kidney, an 8-Fr. mono-J catheter was introduced through the ureter. Irrigation was performed using a pressure-controlled, combined irrigation/suction pump (Uromat E.A.S.I., Karl Storz, Tuttlingen, Germany) in either single-flow or continuous-flow (=combination of irrigation and suction) mode. Intrarenal pressure was measured and irrigation fluid turnover was measured by a cystometry catheter inserted trans-parenchymally into the renal pelvis. Pressure changes were recorded by a urodynamic workstation. RESULTS: Applying pressure-controlled suction, irrigation fluid turnover could be increased by 5 % at an inflow pressure of 75 mmHg (80-84 ml/min) and 15 % at an inflow pressure of 110 mmHg (196-110 ml/min). Suction decreased the intrarenal pressure by 14 % at 75 mmHg (19-14.5 cm H2O) and 28 % at 110 mmHg inflow pressure (37-26.5 cm H2O). CONCLUSION: Although combination of pressure irrigation with sensor-controlled suction increases irrigation flow in SCPI, the intrarenal pressure could be reduced with combined suction via a transurethral mono-J catheter. This irrigation method in percutaneous surgery is called purging effect.

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.

CCL2 Chemokine as a Potential Biomarker for Prostate Cancer: A Pilot Study.

PURPOSE: Prostate specific antigen is not reliable in diagnosing prostate cancer (PCa), making the identification of novel, precise diagnostic biomarkers important. Since chemokines are associated with more aggressive disease and poor prognosis in diverse malignancies, we aimed to investigate the diagnostic relevance of chemokines in PCa. MATERIALS AND METHODS: Preoperative and early postoperative serum samples were obtained from 39 consecutive PCa patients undergoing radical prostatectomy. Serum from 15 healthy volunteers served as controls. Concentrations of CXCL12, CXCL13, CX3CL1, CCL2, CCL5, and CCL20 were measured in serum by Luminex. The expression activity of CXCR3, CXCR4, CXCR5, CXCR7, CXCL12, CXCL13, CX3CR1, CXCL1, CCR2, CCR5, CCR6, CCR7, CCL2, and CCL5 mRNA was assessed in tumor and adjacent normal tissue of prostatectomy specimens by quantitative real-time polymerase chain reaction. The associations of these chemokines with clinical and histological parameters were tested. RESULTS: The gene expression activity of CCL2 and CCR6 was significantly higher in tumor tissue compared to adjacent normal tissue. CCL2 was also significantly higher in the blood samples of PCa patients, compared to controls. CCL5, CCL20, and CX3CL1 were lower in patient serum, compared to controls. CCR2 tissue mRNA was negatively correlated with the Gleason score and grading. CONCLUSION: Chemokines are significantly modified during tumorigenesis of PCa, and CCL2 is a promising diagnostic biomarker.

Direct comparison of targeted MRI-guided biopsy with systematic transrectal ultrasound-guided biopsy in patients with previous negative prostate biopsies.

OBJECTIVE: To directly compare the diagnostic performance of targeted MRI-guided biopsy (MR-GB) and systematic transrectal ultrasound-guided biopsy (TRUS-GB). METHODS: Thirty-five patients with at least one negative TRUS-GB, persistently elevated or rising prostate-specific antigen and a lesion suspicious for prostate cancer (PC) on multiparametric MRI (mpMRI) scored by using the Prostate Imaging Reporting and Data System (PI-RADS) were included. A median of three targeted biopsies per lesion were obtained and systematic TRUS-GB was performed subsequently by an independent urologist without knowledge of the MRI findings. Definite pathology reports were analyzed for anatomical location and criteria of clinical significance. RESULTS: The tumor detection rate was significantly higher with MR-GB compared with TRUS-GB (16/35, 46% and 8/35, 23%, respectively, p < 0.05). MR-GB detected PC in all patients with positive TRUS-GB. All tumors detected by MR-GB exhibited at least one criterion of clinical significance. PC lesions showed a significantly higher PI-RADS sum score compared with benign lesions. CONCLUSIONS: MR-GB is more effective compared with TRUS-GB in detecting clinically significant PC in men after previous negative TRUS-GB. PI-RADS scores give additional information and could be part of the decision-making process when considering retrial biopsy. Additional systematic biopsy can be omitted in patients undergoing targeted MR-GB.

Can high-spatial resolution T2-weighted endorectal MRI rule out clinically significant prostate cancer?

PURPOSE: To evaluate whether clinically significant prostate cancer (PCa) can be ruled out by high-spatial resolution T2-weighted endorectal MRI (eMRI) in a cohort of patients with biopsy-proven PCa. PATIENTS AND METHODS: A retrospective analysis was carried out for consecutive patients who underwent 1.5 Tesla eMRI for local staging before open radical prostatectomy. The cohort was dichotomized into patients with apparent or inapparent tumour on eMRI. The results were compared with final histopathology, and an analysis for presence of clinically significance PCa was performed. RESULTS: A total of 385 patients were included in the study; in 85 patients (22 %), no apparent lesion suspicious for PCa was detected on eMRI, still final pathology revealed clinically significant PCa in 61 of these patients (72 %). In contrast, 256 (85 %) of the 300 patients with apparent tumour in eMRI harboured clinically significant PCa. eMRI could not differentiate clinically significant from insignificant PCa in neither of the groups (p > 0.6). CONCLUSIONS: Presence of clinically significant cancer cannot be excluded by high-resolution 1.5 Tesla T2-weighted eMRI. The results of the study suggest that the role of T2-weighted eMRI for selecting patients suitable for AS is limited.