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Background: Guidelines on the clinical management of non-metastatic castrate-resistant prostate cancer (nmCRPC) generally focus on the need to continue androgen deprivation therapy and enrol patients into clinical trials of investigational agents. This guidance reflects the lack of clinical trial data with established agents in the nmCRPC patient population and the need for trials of new agents. Aim: To review the evidence base and consider ways of improving the management of nmCRPC. Conclusion: Upon the development of castrate resistance, it is essential to rule out the presence of metastases or micrometastases by optimising the use of bone scans and possibly newer procedures and techniques. When nmCRPC is established, management decisions should be individualised according to risk, but risk stratification in this diverse population is poorly defined. Currently, prostate-specific antigen (PSA) levels and PSA doubling time remain the best method of assessing the risk of progression and response to treatment in nmCRPC. However, optimising imaging protocols can also help assess the changing metastatic burden in patients with CRPC. Clinical trials of novel agents in nmCRPC are limited and have problems with enrolment, and therefore, improved risk stratification and imaging may be crucial to the improved management. The statements presented in this paper, reflecting the views of the authors, provide a discussion of the most recent evidence in nmCRPC and provide some advice on how to ensure these patients receive the best management available. However, there is an urgent need for more data on the management of nmCRPC. [ABSTRACT FROM AUTHOR]

In the last few years, the consumption of dietary supplements, especially those having plants as ingredients, has been increasing due to the common idea that they are natural products posing no risks to human health. In the European Union and the United States, dietary supplements are legally considered as foods/special category of foods, thus are not being submitted to any safety assessment prior to their commercialization. Among the issues that can affect safety, adulteration by the illegal addition of pharmaceutical substances or their analogs is of major concern since unscrupulous producers can falsify these products to provide for quick effects and to increase sales. This review discusses the various classes of synthetic drugs most frequently described as being illegally added to dietary supplements marketed for weight loss, muscle building/sport performance and sexual performance enhancement. Information regarding regulation and consumption is also presented. Finally, several conventional and advanced analytical techniques used to detect and identify different adulterants in dietary supplements and therefore also in foods, with particular emphasis on plant food supplements, are critically described. This review demonstrates that dietary supplement adulteration is an emerging food safety problem and that an effective control by food regulatory authorities is needed to safeguard consumers. [ABSTRACT FROM AUTHOR]

Prostate cancer is diagnosed mostly in men over the age of 50 years, and has favorable 5-year survival rates due to early cancer detection and availability of curative surgical management. However, progression to metastasis and emergence of therapeutic resistance are responsible for the majority of prostate cancer mortalities. Recent advancement in sequencing technologies and computational capabilities have improved the ability to organize and analyze large data, thus enabling the identification of novel biomarkers for survival, metastatic progression and patient prognosis. Large-scale sequencing studies have also uncovered genetic and epigenetic signatures associated with prostate cancer molecular subtypes, supporting the development of personalized targeted-therapies. However, the current state of mainstream prostate cancer management does not take full advantage of the personalized diagnostic and treatment modalities available. This review focuses on interrogating biomarkers of prostate cancer progression, including gene signatures that correspond to the acquisition of tumor lethality and those of predictive and prognostic value in progression to advanced disease, and suggest how we can use our knowledge of biomarkers and molecular subtypes to improve patient treatment and survival outcomes.

Purpose: Focal therapy has been proposed as an alternative method to whole-gland treatment for prostate cancer when aiming to reduce treatment side effects. The authors recently validated a radiobiological model which takes into account tumor location and tumor characteristics including tumor cell density, Gleason score, and hypoxia in order to plan optimal dose distributions for focal therapy. The authors propose that this model can be informed using multiparametric MRI (mpMRI) and in this study present a registration framework developed to map prostate mpMRI and histology data, where histology will provide the "ground truth" data regarding tumor location and biology. The authors aim to apply this framework to a growing database to develop a prostate biological atlas which will enable MRI based planning for prostate focal therapy treatment. Methods: Six patients scheduled for routine radical prostatectomy were used in this proof-of-concept study. Each patient underwent mpMRI scanning prior to surgery, after which the excised prostate specimen was formalin fixed and mounted in agarose gel in a custom designed sectioning box. T2-weighted MRI of the specimen in the sectioning box was acquired, after which 5 mm sections of the prostate were cut and histology sections were microtomed. A number of image processing and registration steps were used to register histology images with ex vivo MRI and deformable image registration (DIR) was applied to 3D T2w images to align the in vivo and ex vivo MRI data. Dice coefficient metrics and corresponding feature points from two independent annotators were selected in order to assess the DIR accuracy. Results: Images from all six patients were registered, providing histology and in vivo MRI in the ex vivo MRI frame of reference for each patient. Results demonstrated that their DIR methodology to register in vivo and ex vivo 3D T2w MRI improved accuracy in comparison with an initial manual alignment for prostates containing features which were readily visible on MRI. The average estimated uncertainty between in vivo MRI and histology was 3.3 mm, which included an average error of 3.1 mm between in vivo and ex vivo MRI after applying DIR. The mean dice coefficient for the prostate contour between in vivo and ex vivo MRI increased from 0.83 before DIR to 0.93 after DIR. Conclusions: The authors have developed a registration framework for mapping in vivo MRI data of the prostate with histology by implementing a number of processing steps and ex vivo MRI of the prostate specimen. Validation of DIR was challenging, particularly in prostates with few or mostly linear rather than spherical shaped features. Refinement of their MR imaging protocols to improve the data quality is currently underway which may improve registration accuracy. Additional mpMRI sequences will be registered within this framework to quantify prostate tumor location and biology. [ABSTRACT FROM AUTHOR]

The article presents abstracts related to endourology including "Influence of the platelet rich plasma injections on the urethral anastomosis in mini pigs," by V. V. Lysenko and colleagues, "Is urinary lithogenic risk increasing over the time in patients with urolithiasis?," by H. W. Kang and colleagues, and "Renal colic incidence and its relation to climate," by M. Ahrari and colleagues.

Objective: To evaluate the feasibility of prostate histoscanning true targeting (PHS-TT) guided transrectal ultrasound (TRUS) biopsy. Methods: This is a prospective, single center, pilot study performed during February 2013-September 2013. All consecutive patients planned for prostate biopsy were included in the study, and all the procedure was performed by a single surgeon aided by the specialized true targeting software. Initially, the patients underwent PHS to map the abnormal areas within the prostate that were ≥0.2 cm. TRUS guided biopsies were performed targeting the abnormal areas with a specialized software. Additionally, routine bisextant biopsies were also taken. The final histopathology of the target cores was compared with the bisextant cores. Results: A total of 43 patients underwent combined 'targeted PHS guided' and 'standard 12 core systematic' biopsies. The mean volume of abnormal area detected by PHS is 4.3 cm. The overall cancer detection rate was 46.5 % (20/43) with systemic cores and target cores detecting cancer in 44 % (19/43) and 26 % (11/43), respectively. The mean % cancer/core length of the PHS-TT cores were significantly higher than the systematic cores (55.4 vs. 37.5 %. p < 0.05). In biopsy naïve patients, the cancer detection rate (43.7 % vs. 14.8 %. p = 0.06) and the cancer positivity of the cores (30.1 vs. 6.8 %. p < 0.01) of target cores were higher than those patients with prior biopsies. Conclusion: PHS-TT is feasible and can be an effective tool for real-time guidance of prostate biopsies. [ABSTRACT FROM AUTHOR]

Background: A growing number of treatment options exist to treat metastatic castrate-resistant prostate cancer (mCRPC), and with these newer options, many questions about optimising treatment remain unanswered. One recommendation that may potentially be overlooked by practitioners is that androgen deprivation therapy (ADT) should be maintained when CRPC develops and when treatment with any of the newer agents is initiated. Aim: However, to emphasise this recommendation, it is valuable to interrogate the evidence for maintaining ADT in different clinical situations. Outcome: This statement, reflecting the views of the authors, provides a discussion of this evidence and the rationale behind the recommendation that ADT should be continued in CRPC. [ABSTRACT FROM AUTHOR]

A design space approach was applied to optimize the extraction process of Danhong injection. Dry matter yield and the yields of five active ingredients were selected as process critical quality attributes (CQAs). Extraction number, extraction time, and the mass ratio of water and material (W/M ratio) were selected as critical process parameters (CPPs). Quadratic models between CPPs and CQAs were developed with determination coefficients higher than 0.94. Active ingredient yields and dry matter yield increased as the extraction number increased. Monte-Carlo simulation with models established using a stepwise regression method was applied to calculate the probability-based design space. Step length showed little effect on the calculation results. Higher simulation number led to results with lower dispersion. Data generated in a Monte Carlo simulation following a normal distribution led to a design space with a smaller size. An optimized calculation condition was obtained with 10000 simulation times, 0.01 calculation step length, a significance level value of 0.35 for adding or removing terms in a stepwise regression, and a normal distribution for data generation. The design space with a probability higher than 0.95 to attain the CQA criteria was calculated and verified successfully. Normal operating ranges of 8.2-10 g/g of W/M ratio, 1.25-1.63 h of extraction time, and two extractions were recommended. The optimized calculation conditions can conveniently be used in design space development for other pharmaceutical processes. [ABSTRACT FROM AUTHOR]

This manuscript demonstrates a Quality by Design approach using Design of Experiments to prove the robustness of a stability indicating HPLC method. The method determines the omeprazole in the presence of eight related substances and ketoprofen with six impurities developed for pellets filled capsule as a combined finished drug product. Based on the results, controllable factors that have influential effect on the resolution between peaks were identified and were examined while blocking the uncontrollable factors. The design employs a full factorial design of experiment for the interaction of controllable factors. A flowchart parades all steps of QbD approach by blocking and varying certain factors. Thus, the primary objective of this manuscript is to demonstrate the method's robustness by clarifying various steps systematically. [ABSTRACT FROM AUTHOR]

The detection, confirmation, and quantification ofmultiple illegal adulterants in health foods and herbalmedicines by using a single analytical method are a challenge. This paper reports on a new strategy to meet this challenge by employing high-performance liquid chromatography coupled with high-resolution mass spectrometry and a mass spectral tree similarity filter technique. This analytical method can rapidly collect high-resolution, high-accuracy, optionally multistage mass data for compounds in samples. After a preliminary screening by retention time and high-resolution mass spectral data, known illegal adulterants can be detected. The mass spectral tree similarity filter technique has been applied to rapidly confirm these adulterants and simultaneously discover unknown ones. By using full-scan mass spectra as stem and data-dependent subsequent stage mass spectra to form branches, mass spectrometry data from detected compounds are converted into mass spectral trees. The known or unknown illegal adulterants in the samples are confirmed or discovered based on the similarity between their mass spectral trees and those of the references in a library, and they are finally quantified against standard curves. This new strategy has been tested by using 50 samples, and the illegal adulterants were rapidly and effectively detected, confirmed and quantified. [ABSTRACT FROM AUTHOR]

A considerable number of erectile dysfunction products, and dietary supplements suspected of containing phosphodiesterase-5 (PDE-5) inhibitors, have been analyzed by the US Food and Drug Administration. Often these samples are found to contain the approved active pharmaceutical ingredients (APIs) such as sildenafil, tadalafil or vardenafil. However, analogs of these APIs have also been identified in many samples and products containing multiple PDE-5 inhibitors have also been found. A single high-performance liquid chromatography with ultraviolet detection method has been developed for the determination of sildenafil, tadalafil, vardenafil and a number of commonly encountered analogs in pharmaceutical dosage forms and dietary supplement products, including tablets, capsules, bulk powders, troches and liquids. This method was designed as an alternative to methods developed for the determination of a single PDE-5 inhibitor. Using this protocol, 14 PDE-5 inhibitor compounds can be separated and determined in a single analysis. [ABSTRACT FROM AUTHOR]

Being considered a 'liquid biopsy', circulating tumor cell (CTC) quantification is of great interest for evaluating cancer dissemination, predicting patient prognosis, and also for the evaluation of therapeutic treatments, representing a reliable potential alternative to invasive biopsies and subsequent proteomic and functional genetic analysis. Compared to a biopsy, the gold standard of current cancer diagnosis, an important characteristic of a blood test is that it is safe and can be performed at many points during the disease, allowing the development of appropriate therapy modifications and potentially improving patient's quality of life. In this work, an ultrasensitive electrochemical telomerase activity-sensing strategy is presented that utilizes DNA-templated deposition of silver nanoparticles as electroactive labels through a highly sharp solid-state Ag/AgCl reaction with DNA exonuclease III-assisted background current suppression. This nanoparticle-mediated signal amplification resulted in significantly decreased detection limit, which is better than the vast majority of reported methods and achieves a sensitivity comparable to the conventional telomeric repeat amplification protocol (TRAP). This work may pave a new PCR-free way for the detection of telomerase activity in CTCs via a noninvasive routine blood test for point-of-care diagnosis and individualized treatment of cancer. [ABSTRACT FROM AUTHOR]

Purpose : To assess the impact of micropapillary histological variant on oncological outcome after radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinomas (UTUCs). Methods: A French multicenter retrospective study was performed on patients who underwent RNU between 1995 and 2010. Pathological reports were reviewed to identify patients with pure urothelial carcinomas (PUC) and those with micropapillary histological variant (MPC). Uni- and multivariate Cox regression analyses were performed to identify factors predictive of survival. Results: Overall, 519 patients were included and divided into two groups: 480 PUC and 39 MPC. Median follow-up were 28 and 19 months, respectively ( p = 0.63). There was no difference between the two groups for gender, age and tumor location (pelvicalyceal or ureteral). MPC was associated with high-stage and high-grade UTUC ( p < 0.001 and 0.04). No difference was observed between the two groups for 5-year cancer-specific survival (76.1 vs. 88.2 %; p = 0.54). The 5-year metastasis-free survival was significantly lower in the MPC group (48.9 vs. 73.8 %; p = 0.037). In multivariate analysis, pT stage, lymphovascular invasion, margin status and adjuvant chemotherapy administration were independent predictors of specific survival ( p = 0.002; 0.001; 0.02; 0.01), contrary to histological variant ( p = 0.94). Conclusions: Micropapillary histological variant was associated with advanced UTUC and reduced metastasis-free survival after RNU. It should be considered as an aggressive tumor and thus be stated in any pathological report after radical surgery. [ABSTRACT FROM AUTHOR]

Purpose: Cancer is the leading cause of death among patients aged 65 years and older. In this population, the cancer diagnosis is often made at a more advanced stage and worse prognosis than in younger patients. Specific mortality in older patients is superior to that reported in their younger counterparts. Moreover, the impact of curative treatment that has proven benefit in overall population may be not well studied in the sub-group of older patients. Thus, the management of cancer in the elderly is a major public health concern in most Western countries. Methods/results: In this review, we summarize this challenging treatment decision-making in older urologic patients with prostate, kidney or bladder cancer. The estimation of life expectancy remains a difficult task. Chronological age should not be considered as the main decisive factor anymore when considering aggressive cancer treatment. Comorbidities increase the complexity of cancer management and affect survival. Multidisciplinary evaluation and comprehensive geriatrics assessment using specific scales are critical to improve the treatment decision-making and to minimize both overtreatment of low-risk disease and undertreatment of high-risk disease. When an aggressive and potential quality-of-life-threatening treatment is scheduled after this comprehensive geriatrics assessment, personalized patient care must be early predefined by the geriatric team. Conclusions: In the elderly, an enhanced support including specific geriatric assessment and management optimizes the treatment course, including preoperative optimization, prevents treatment-related complications and loss of autonomy using or not geriatrics clinic or rehabilitation units, and limits the length of hospital stay and costs. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the long-term outcomes of patients with prostate cancer who have pathological pT3b N0-Nx, with postoperative PSA < 0.1 ng/ml and no systematic adjuvant treatment. Materials and methods: Using a monocentric prospectively maintained database, we identified among 2,142 men who underwent minimally invasive radical prostatectomy, 104 pT3b N0-Nx patients, with postoperative PSA < 0.1 ng/ml and at least 5 years of follow-up. Patients were considered for salvage treatment at biochemical recurrence (PSA ≥ 0.2 ng/ml). Results: The median time of follow-up was 83.5 months (interquartile range [IQR]: 69-99). Overall, 102 patients (98 %) had T2 clinical stage or less. Specimen Gleason score was 7 in 71 patients (68 %) and <7 in 15 (14 %). Thirty-eight patients (37 %) were upgraded for Gleason score after radical prostatectomy. The overall 5-year probability of freedom from biochemical recurrence for the entire cohort was 55.8 % (95 % CI 45.8-65.8) and 73.3 % for patients who had specimen Gleason score <7 ( p = 0.005). In univariate analysis, specimen Gleason score and surgical margin status were significant predictors for biochemical failure after radical prostatectomy ( p = 0.05 and 0.007, respectively). In multivariate analysis, only specimen Gleason score >7 was significantly associated with biochemical failure ( p = 0.009). Conclusion: SVI is an adverse prognostic factor, but it is not associated with a uniformly poor prognosis. Specimen Gleason score and surgical margin status are significant predictors of recurrence after radical prostatectomy in patients with prostate cancer and SVI. [ABSTRACT FROM AUTHOR]

An in vitro steroidogenesis assay using H295R human adenocarcinoma cells is a useful tool for the fast identification of compounds that affect the production of testosterone and 17β-estradiol. Selective and sensitive hormone measurement by liquid chromatography–tandem mass spectrometry (LC–MS/MS) can make this assay more reliable. Therefore, in the present study, a sensitive and selective method for the quantification of testosterone and 17β-estradiol in the H295R steroidogenesis assay was developed and fully validated using LC–MS/MS coupled with an online sample enrichment technique. To prove its usefulness, the method developed was applied to investigate the effect of sildenafil on steroidogenesis. Cell medium samples were diluted and prepared using solid-phase extraction. The samples were prepared on ice and were not kept for more than 30 min to prevent degradation of hormones. The extracts were dried, reconstituted, filtered, and analyzed by LC–MS/MS with polarity switching electrospray ionization. The validation results for selectivity, matrix effect, recovery, linearity, precision, and accuracy were satisfactory. The limits of detection for testosterone and 17β-estradiol were 5 and 10 pg/mL, respectively, and the limit of quantification for both testosterone and 17β-estradiol was 10 pg/mL, which was in accordance with the OECD guideline. No degradation was observed under the storage conditions for 7 and 14 days at -80 °C as well as after three freeze–thaw cycles, whereas 17β-estradiol was degraded after 1 h on ice during sample processing. The method developed was successfully used for the investigation of the effect of sildenafil on steroidogenesis. This method can be very useful for the initial selection of drugs with androgenic and/or estrogenic effects for specific purposes, e.g., in the selection of drugs that are used to reverse the effects of chemical castration. [ABSTRACT FROM AUTHOR]

Objectives: To review the current literature about prostate-sparing radical cystectomy (PSRC) and its potential for management of a selected population of patients with bladder cancer. Materials and Methods: The PubMed, EMBASE and Scopus databases were searched for the key words 'prostate', 'sparing' and 'cystectomy' between 1984 and 2012. Articles in English, French and German were considered relevant for review. Institutional experience with this procedure was also included. Results: PSRC remains a controversial procedure for the treatment of patients harboring bladder carcinoma, mainly due to insufficient knowledge of clear indications and/or contraindications. Experience with PSRC is still limited to very few referral centers and there is a lack of large series with long-term outcomes. The potential for excellent functional outcomes must be carefully balanced against inconsistent oncological results. Conclusions: PSRC may become an option for carefully selected and extensively informed patients. Suggestions for possible indications and contraindications are presented. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The chemical castration law, which targets child molesters with recidivism, was introduced in Korea in 2011. For this, leuprolide, a gonadotropin-releasing hormone agonist, is used to decrease testosterone production and suppress libido. In order to achieve efficient law enforcement, it is necessary to monitor intentional ingestion of drugs that antagonize the effect of leuprolide. Therefore, an analytical method for the simultaneous detection of mirodenafil, sildenafil, tadalafil, udenafil, vardenafil, icariin, alprostadil, and yohimbine, which are the major impotence treatment drugs, legitimately or otherwise, in Korea, as well as their selected metabolites, in human urine was established and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). First, different sample preparation methods, two solid-phase extractions with different cartridges and protein precipitation, were compared and protein precipitation was chosen for the entire study because it showed better matrix effects and recoveries. Thus, the drugs and metabolites in urine were extracted by protein precipitation and then filtered and analyzed by LC-MS/MS with polarity switching electrospray ionization. The validation results of selectivity, matrix effect, recovery, linearity, intra- and inter-assay precision and accuracy were satisfactory. The limits of detection ranged from 0.25 to 10 ng/mL, and the limits of quantification were 2.5 to 50 ng/mL. The drugs and metabolites in urine did not show any degradation under storage for 7 and 15 days at 4 and −20 °C as well as after three freeze-thaw cycles. The developed method will be very useful for monitoring the illegal use of impotence treatment drugs. [ABSTRACT FROM AUTHOR]

The detection of regulated and forbidden herbs in pharmaceutical preparations and nutritional supplements is a growing problem for laboratories charged with the analysis of illegal pharmaceutical preparations and counterfeit medicines. This article presents a feasibility study of the use of chromatographic fingerprints for the detection of plants in pharmaceutical preparations. Fingerprints were developed for three non-regulated common herbal products- Rhamnus purshiana, Passiflora incarnata L. and Crataegus monogyna-and this was done by combining three different types of detection: diode-array detection, evaporative light scattering detection and mass spectrometry. It is shown that these plants could be detected in respective triturations of the dry extracts with lactose and three different herbal matrices as well as in commercial preparations purchased on the open market. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Objectives: To identify predictive factors and assess the impact on oncological outcomes of intravesical recurrence after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC). Methods: Using a national multicentric retrospective dataset, we identified all patients with UTUC who underwent a RNU between 1995 and 2010 ( n = 482). Intravesical recurrence was tested as a prognostic factor for survival through univariable and multivariable Cox regression analysis. Results: Overall, intravesical recurrence occurred in 169 patients (35 %) with a median age of 69.2 years (IQR: 60-76) and after a median follow-up of 39.5 months (IQR: 25-60). Actuarial intravesical recurrence-free survival estimates at 2 and 5 years after RNU were 72 and 45 %, respectively. On univariable analyses, previous history of bladder tumor, tumor multifocality, laparoscopic approach, pathological T-stage, presence of concomitant CIS and lymphovascular invasion were all associated with intravesical recurrence. On multivariable analysis, previous history of bladder cancer, tumor multifocality and laparoscopic approach remained independent predictors of intravesical recurrence. Existence of intravesical recurrence was not correlated with worst oncological outcomes in terms of disease recurrence ( p = 0.075) and cancer-specific mortality ( p = 0.06). Conclusions: In the current study, intravesical recurrence occurred in 35 % of patients with UTUC after RNU. Previous history of bladder cancer, tumor multifocality, concomitant CIS and laparoscopic approach were independent predictors of intravesical recurrence. These findings are in line with recent published data and should be considered carefully to provide a definitive surveillance protocol regarding management of urothelial carcinomas regardless of the location of urothelial carcinomas in the whole urinary tract. [ABSTRACT FROM AUTHOR]

Objectives: Recent publications have assessed the prognostic significance of hydronephrosis in the outcome of upper tract urothelial carcinoma (UUT-UC). Our study sought to determine the prognostic impact of hydronephrosis on UUT-UC survival and its relationship to the clinicopathological features. Materials and methods: A retrospective, multi-institutional French study was conducted on 401 patients who underwent radical nephroureterectomy for non-metastatic UUT-UC. Hydronephrotic status was determined using preoperative imaging reports. Univariate and multivariate analyses were conducted to identify factors associated with survival. Results: Preoperative hydronephrosis was present in 74 patients. Median follow-up was 26 months. Hydronephrosis was associated only with ureteral localisation ( p < 0.001). No difference was observed in 5-year cancer-specific survival (CSS) between the hydronephrosis group (80.1 %) and the no hydronephrosis group (83.6 %) ( p > 0.05). Only age ( p = 0.02) and pT stage ( p = 0.01) were independent predictors of CSS. Hydronephrosis was not a significant predictor of CSS in the univariate and multivariate analyses ( p = 0.87 and p = 0.66). No significant difference was observed for 5-year metastasis-free survival (MFS) between the hydronephrosis group (69.8 % ± 6.6 %) and the no hydronephrosis group (80.5 % ± 3 %) ( p = 0.052). Hydronephrosis was not a significant predictor of MFS in the univariate and multivariate analyses ( p = 0.16 and p = 0.36). Multifocality ( p = 0.02), pT stage ( p < 0.001) and positive surgical margins ( p = 0.02) were independent predictors of MFS. For the pelvic tumours subgroup, hydronephrosis was an independent predictor of MFS ( p = 0.01) but not CSS ( p = 0.86). Conclusion: Preoperative hydronephrosis was not associated with survival. However, among tumours presenting with hydronephrosis, pelvicalyceal tumours appear to have a worse prognosis than ureteral tumours. [ABSTRACT FROM AUTHOR]

An ultra-fast liquid chromatography-electrospray ionization tandem mass spectrometry method was developed and validated to simultaneously screen, confirm, and determine 18 illegal adulterants in herbal medicines and health foods for male sexual potency. The separation was achieved on a Shim- Pack XR- ODS II column (2.0 × 100 mm, 2.2 μm) with acetonitrile and aqueous solution (12 mmol/L ammonium formate, 0.01% acetic acid) as mobile phase at a flow rate of 0.4 mL/min with a gradient elution. The column temperature was maintained at 40°C and the run time was within 18 min. The 18 illegal adulterants were detected in electrospray ionization positive mode by multiple-reaction monitoring. All the calibration curves showed good linearity with correlation coefficient ( r) higher than 0.996 within the tested concentration ranges. The extraction recoveries and relative recoveries were in the range of 79.5-114% and 82.0-120%, respectively. The RSD of repeatability and intermediate precision was all less than 18% and the accuracy was in the range of 81.7-118%. The intra-day and inter-day stability was in the range of 86.8-110%. The validated method was successfully applied to screen, confirm, and determine 16 samples. Nine products were confirmed to contain illegal adulterants and the contents of adulterants were related to the therapeutic dosages. [ABSTRACT FROM AUTHOR]

Context: The accessibility of pharmacies in neighboring countries has facilitated the trend of acquiring medications outside of local borders. However, scientific data assessing the drug content and quality of these medications has not increased in a corresponding fashion. Objective: This study seeks to augment existing scientific data. Materials and methods: Seventeen products that were obtained from pharmacies in Mexico were evaluated for active ingredient content. The active pharmaceutical ingredients (API) assessed included amoxicillin, ampicillin, ciprofloxacin, levothyroxine, sildenafil citrate, sulfamethoxazole, trimethoprim, and warfarin. API content was analysed with high performance liquid chromatography assays and the resultant data interpreted by applying United States Pharmacopeia (USP) acceptability limits. Results: All of the samples analyzed for the two ciprofloxacin products and the two ampicillin products were found to be within the USP limits. Of the four different sulfamethoxazole/trimethoprim products tested, all were within USP limits for sulfamethoxazole, but contained 2-3 individual units which were outside of USP limits for trimethoprim. Several of the remaining products (amoxicillin, levothyroxine, sildenafil citrate, and warfarin) had individual units that fell outside of the USP limits, although only one of the levothyroxine products (1 out of 20 tablets tested) and both sildenafil citrate products (all of the units tested) contained units outside of ±25% label claim. [ABSTRACT FROM AUTHOR]

Current criteria to predict low-risk prostate cancer (PCa) are still subject to discussion as a substantial number of PCa patients who progress to a more aggressive disease seem to be missed, using these criteria. The main challenge in PCa diagnosis, therefore, is to distinguish patients with low-risk PCa who will show slow progression of disease from patients at risk for progression to a more aggressive cancer. The current discovered biomarkers could potentially guide in this management and improve detection, staging, and prognosis. This paper provides an overview of the current available serum-, urine-, and tissue-based biomarkers in PCa and evaluates the clinical usefulness of these biomarkers in the detection and management of low-risk PCa. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate the midterm oncologic results of extraperitoneal laparoscopic radical prostatectomy (EPLRP) for Asian men with localized prostate cancer. Methods. Between 2004 and 2009, 218 men underwent EPLRP at an Asian tertiary hospital. The mean preoperative prostate-specific antigen (PSA) was 15.5 ng/ml andmean Gleason score was 6.6. Stage distributions were cT1a-b in 21 cases, cT1c in 139, cT2 in 48 and cT3 in 10. Disease recurrence was defined as PSA≥0.2 ng/mL in 2 consecutive measurements or initiation of secondary therapy. Results. Postoperative pathological stage was pT2a-b in 33 patients, pT2cN0 in 10, pT3a in 27, pT3b in 36, pT4 in 9 and pN1 in 10. Positive surgical margins occurred in 14.6% and 48.6% for pT2 and pT3 diseases, respectively (P < .001). The overall PSA recurrence-free survival at 3 and 5 years was 82.1% and 74.5%. By the pathological stages, 3-year recurrence-free survival was 92.4% (pT2), 81.1% (pT3a), 62.6% (pT3b-4) and 55.6% (pN1), respectively (P < .001). Conclusions. EPLRP is curative even for some locally advanced prostate cancers in a midterm follow-up. Even at an Asian center of low volume of radical prostatectomy EPLRP still provides oncologic outcomes similar to that of high volume centers. [ABSTRACT FROM AUTHOR]

Although rectourinary fistula (RUF) after radical prostatectomy (RP) is rare, it is an important issue impairing the quality of life of patients. If the RUF does not spontaneously close after colostomy, surgical closure should be considered. However, there is no standard approach and no consensus in the literature. A National Center for Biotechnology Information (NVBI) PubMed search for relevant articles published between 1995 and December 2010 was performed using themedical subject headings "radical prostatectomy" and "fistula." Articles relevant to the treatment of RUF were retained. RUF developed in 0.6% to 9% of patients after RP. Most cases required colostomy, but more than 50% of them needed surgical fistula closure thereafter. The York-Mason technique is the most common approach, and closure using a broad-based flap of rectal mucosa is recommended after excision of the RUF. New techniques using a sealant or glue are developing, but further successful reports are needed. [ABSTRACT FROM AUTHOR]

A positive surgical margin at prostatectomy is defined as tumor cells touching the inked edge of the specimen. This finding is reported in 8.8% to 42% of cases (median about 20%) in various studies. It is one of the main determinants of eventual biochemical (PSA) failure, generally associated with a doubled or tripled risk of failure. The effect of a positive margin on outcome can be modified by stage or grade and the length, number and location of positivemargins, as well as by technical operative approach and duration of operator experience. This paper tabulates data from the past decade of studies on margin status. [ABSTRACT FROM AUTHOR]

Objective. The aim of the present study was to evaluate initial learning curves of laparoscopic radical prostatectomy (LRP) with regard to complications, urinary continence, and oncologic outcome. Materials and Methods. We retrospectively reviewed 100 consecutive patients with clinically localized prostate cancer. All 100 patients underwent LRP performed by the same urologist at one institution. Results: Mean operating time (208.4 ± 48.6min), estimated blood loss (495.8 ± 436.5mL), allogeneic blood transfusion rate (0%), and intraoperative complications diminished with surgical experience. Positive margin rate varied greatly among pathological stage (positive margin rates: pT2 = 20.5%; pT3 = 63.0%). A trend towards reduction of positive surgical margins in pT2 cases was apparent with increasing experience. Intraoperative and early complications occurred in 2.0% of patients. In all patients, 85.9% used none or no more than one pad per 24 h at 6months postoperatively. Prostate-specific antigen recurrence was seen in only 2 patients. Conclusions. In the present series of 100 patients, our retrospective evaluation confirms that LRP provides satisfactory results. [ABSTRACT FROM AUTHOR]

Traditionally, the patient with a new diagnosis of localized prostate cancer faces either radical therapy, in the form of surgery or radiation, or active surveillance. A growing subset of these men may not be willing to accept the psychological burden of active surveillance nor the side effects of extirpative or radiation therapy. Local ablative therapies including cryotherapy, high-intensity focused ultrasound, and vascular-targeted photodynamic therapy have emerged as a means for minimally invasive definitive treatment. These treatments are well tolerated with decreased morbidity in associationwith improvements in technology; however, long-term oncologic efficacy remains to be determined. [ABSTRACT FROM AUTHOR]

Laparoscopic extraperitoneal radical prostatectomy (LERP) is considered the standard care treatment option for the management of localized and locally advanced prostatic cancer (PCa) in many institutes worldwide. In this work, the main advantages and disadvantages of LERP approach are reviewed with regard to its outcomes, the complication management, the learning curve, and the extend of pelvic lymph node dissection (PLND). It is concluded that LERP demonstrates comparable cancer control, urinary continence, and potency outcomes with the open and the robot-assisted radical prostatectomy, while offering advantages in complication management in comparison to the transperitoneal approach. Learning curve of LERP is considered long and stiff and significantly affects perioperative outcomes and morbidity, cancer control, and functional results. Thus, close mentoring especially in the beginning of the learning curve is advised. Finally, LERP still has a role in the limited or modified PLND offered in intermediate risk PCa patients. [ABSTRACT FROM AUTHOR]

Introduction. Recto-urinary fistulas resulting from trauma or surgery are a serious and debilitating complication. They represent a challenge not only because of the difficulty on choosing the best technique to solve them but also because of the risk of recurrence. Spontaneous cure is rare. Materials and Methods. We describe the case of a 61-years-old man that on the 9th postoperative day of a laparoscopic radical prostatectomy (LRP) started with fecaluria and liquid faeces. Recto-urinary fistula was confirmed at the 10th postoperative day by CT scan and contrast enema. Discussion. We chose the York-Mason technique, because it is simple to perform, effective and has minimal morbidity. This is a posterior, transrectal, and transsphincteric approach, carried out on healthy tissues without previous scarring phenomena. Results. The postoperative period progressed without complications, and the patient discharged on the 4th day. The closure of the fistula was confirmed radiologically by retrograde cystography after 4 weeks allowing the removal of drainage catheter. The reconstruction of intestinal transit was carried out 2 months later. Conclusion. The York-Mason technique, a transrectal and transsphincteric approach with minimal morbidity, proved to be effective on the resolution of the recto-urinary fistula, a rare complication of the radical prostatectomy. [ABSTRACT FROM AUTHOR]

The article presents information on the research related to the physiology of the lower abdominal tract in the humans. It informs that real time grading of bladder urothelial carcinoma (UC) is clinically important and can only be completed by the Optical Coherence Tomography (OCT). It further informs about the studies related to the physical classification of pelvic region and the comparison of the two electric prostate morcellators.

Contactless dielectrophoresis (cDEP) is a recently developed method of cell manipulation in which the electrodes are physically isolated from the sample. Here we present two microfluidic devices capable of selectively isolating live human leukemia cells from dead cells utilizing their electrical signatures. The effect of different voltages and frequencies on the gradient of the electric field and device performance was investigated numerically and validated experimentally. With these prototype devices we were able to achieve greater than 95% removal efficiency at 0.2–0.5 mm s−1with 100% selectivity between live and dead cells. In conjunction with enrichment, cDEP could be integrated with other technologies to yield fully automated lab-on-a-chip systems capable of sensing, sorting, and identifying rare cells. [ABSTRACT FROM AUTHOR]

An abstract index for the October 2009 issue of the periodical is presented.

To present oncological results with intermittent androgen deprivation (IAD) in a single center. Between 1992 and 2008, 566 patients with prostate cancer (PC) were selected for a non-randomized study of IAD. Two hundred and eighteen patients had biochemical recurrence (BCR) after local treatment for PC and 348 patients had micro- or macro-metastatic disease. On-treatment period (ONTP) consisted of three-monthly injections of gonadatropin-releasing hormone (GnRH) agonist combined with daily oral androgen receptor antagonist. Off-treatment period (OFTP) was indicated when prostate-specific antigen (PSA) was <4 ng/ml. Criteria for resumption of hormonal therapy were PSA >20 ng/ml or clinical symptoms. Cancer specific survival curves were computed according to the Kaplan–Meier method. Median follow-up was 81 months (12–230). Median age was 74.7 years (52–92). Median Gleason score at diagnosis was 7 (3–9). Median initial PSA was 17 ng/ml (0.4–433). Cycle duration decreased progressively from 23 months for the 1st cycle to 10 months at 12th cycle. The number of patients who became hormone resistant was 182 (32%). Median cancer specific survival probability for the series is 12 (10.8–infinity) years. No previous treatment group showed a higher cancer specific survival probability (log rank test, CI 95%, P = 0.003) versus BCR group. Multivariate analysis of cancer specific survival demonstrates age, initial Gleason score and initial PSA level as significant factors affecting mortality ( P < 0.05). Intermittent androgen deprivation is an acceptable treatment in different stages of PC. Duration of cycle decreased progressively during therapy. Age, Gleason score and PSA are factors predicting mortality. [ABSTRACT FROM AUTHOR]

In this study we obtained Fourier transform infrared (FTIR) spectra of fixed prostate cell lines of differing types as well as the primary epithelial cells from benign prostatic hyperplasia (BPH). Results showed that by using multivariate chemometric analysis it was possible to discriminate and classify these cell lines, which gave rise to sensitivity and specificity values of >94% and >98%, respectively. Following on from these results the possible influences of different factors on the discrimination and classification of the prostate cell lines were examined. Firstly, the effect of using different growth media during cell culturing was investigated, with results indicating that this did not influence chemometric discrimination. Secondly, differences in the nucleus-to-cytoplasm (N/C) ratio were examined, and it was concluded that this factor was not the main reason for the discrimination and classification of the prostate cancer (CaP) cell lines. In conclusion, given the fact that neither growth media nor N/C ratio could totally explain the classification it is likely that actual biochemical differences between the cell lines is the major contributing factor. [ABSTRACT FROM AUTHOR]

In this paper we report on preliminary investigations into using Raman tweezers to classify urological cell lines. This builds on earlier work within the group, whereby Raman tweezer methodologies were developed, and the application of this technique to differentiate between live prostate cancer (CaP) and bladder cells lines (PC-3 and MGH-U1 respectively) was demonstrated. In this present study we analysed chemically fixed cells using two different fixative methods; SurePathTM (a commercial available liquid based cytology media) and 4% v/v formalin/PBS fixatives. The study has been expanded from our previous live cell study to include the androgen sensitive CaP cell line LNCaP, primary benign prostate hyperplasia (BPH) cells as well as primary urethral cells. Raman light from the cells was collected using a 514.5 nm Ar-ion laser excitation source in back-scattering configuration mode. Principal component-linear discriminate analysis (PC-LDA) models of resulting cell spectra were generated and these were validated using a blind comparison. Sensitivities and specificities of > 72% and 90% respectively, for SurePath fixed cells, and > 93% and 98% respectively for 4% v/v formalin/PBS fixed cells was achieved. The higher prediction results for the formalin fixed cells can be attributed to a better signal-to-noise ratio for spectra obtained from these cells. Following on from this work, urological cell lines were exposed to urine for up to 12 hours to determine the effect of urine on the ability to classify these cells. Results indicate that urine has no detrimental effect on prediction results. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

To assess the oncological safety of laparoscopic procedures for the management of urothelial carcinomas of the urinary tract. Data on laparoscopic management of urothelial carcinomas in the literature were analysed using MEDLINE and by matching the following keywords: urological malignancies, upper tract tumours, bladder carcinomas, laparoscopic approach, recurrence, follow-up and metastasis site. Minimally invasive techniques are being used increasingly in the management of these tumours and successfully achieving the benefits of lower blood loss and more rapid patient recovery. To date, no evidence level 1 information is available and published series of these technically challenging cases are small and follow-up limited. Short to medium term follow-up appears encouraging in terms of recurrence and survival rates, but long-term data are immature compared to the established open techniques these procedures seek to duplicate. Specific concerns in terms of the oncologic safety of laparoscopy, especially with regard to the pneumoperitoneum, tumour manipulation and specimen extraction are addressed. Port-site metastases and tumour seeding are rare events and appear to be mainly related to the grade and stage of the tumour. Specific precautions are required to minimise these risks. Oncological results of the laparoscopic approach are difficult to compare with those of open surgery. However, recent series have not reported unusual tumour dissemination or a higher rate of recurrence with this approach. Laparoscopic techniques are not yet standard of care in invasive urothelial carcinomas. Long-term assessment is ongoing and awaited. [ABSTRACT FROM AUTHOR]

Safety concerns exist for potential thermal damage at tissue-air or tissue-bone interfaces located in the post-focal region during high intensity focused ultrasound (HIFU) treatments. We tested the feasibility of reducing thermal energy deposited at the post-focal tissue-air interfaces by producing bubbles (due to acoustic cavitation and/or boiling) at the HIFU focus. HIFU (in-situ intensities of 460–3500 W/cm2, frequencies of 3.2–5.5 MHz) was applied for 30 s to produce lesions (in turkey breast in-vitro (n=37), and rabbit liver (n=4) and thigh muscle in-vivo (n=11)). Tissue temperature was measured at the tissue-air interface using a thermal (infrared) camera. Ultrasound imaging was used to detect bubbles at the HIFU focus, appearing as a hyperechoic region. In-vitro results showed that when no bubbles were present at the focus (at lower intensities of 460–850 W/cm2), the temperature at the interface increased continuously, up to 7.3±4.0 °C above the baseline by the end of treatment. When bubbles formed immediately after the start of HIFU treatment (at the high intensity of 3360 W/cm2), the temperature increased briefly for 3.5 s to 7.4±3.6 °C above the baseline temperature and then decreased to 4.0±1.4 °C above the baseline by the end of treatment. Similar results were obtained in in-vivo experiments with the temperature increases (above the baseline temperature) at the muscle-air and liver-air interfaces at the end of the high intensity treatment lower by 7.1 °C and 6.0 °C, respectively, as compared to the low intensity treatment. Thermal effects of HIFU at post-focal tissue-air interfaces, such as in bowels, could result in clinically significant increases in temperature. Bubble formation at the HIFU focus may provide a method for shielding the post-focal region from potential thermal damage. [ABSTRACT FROM AUTHOR]

The article presents abstracts of medical research. They include "Does teaching affect outcomes of radical prostatectomy," "Multiple molecular markers in the diagnosis of prostate cancer from prostatic fulid," and "Binding characteristics of clinically effective muscarinic antagonists in human bladder detrusor and urothelium."

The aim of this study is to report the relative advantages and disadvantages of the radical prostatectomy with a laparoscopic (LRP) and a robotic (RALP) approach. A medline search was performed. Published data regarding perioperative parameters, complications, oncological results, functional results were analyzed. Shorter learning curves have been reported with the RALP. Intra-operative and post-operative outcomes appear to be comparable between the two approaches. The average time for LRP is 234 min (151–453) versus 182 min (141–250) for RALP. Estimated blood loss for the LRP averages 482 ml (185–850) versus 234 ml (75–500) for the RALP. Complication rates in single institution studies are similar. Long-term outcomes data on PSA progression is not yet available for LRP or RALP due to their relatively short existence. RALP appears to offer a significant benefit to the laparoscopically naïve surgeon with respect to learning curve when compared to LRP. This, however, comes at an increased cost. Intra-operative and post-operative outcomes appear to be similar. Longer follow-up data is necessary to compare oncological and functional outcomes. [ABSTRACT FROM AUTHOR]

Pilot calculations have been performed to study the effect of surrounding plasma on several doubly excited states for a few astrophysically important, highly stripped ions of helium isoelectronic sequence Al11+, Si12+, P13+, S14+, and Cl15+. The transitions from 1s2:1Se → 2s2:1Se, 2p2:1De, 2s2p:1Po, 2s3d:1De and 2p3d:1Fo are studied. The effect of the plasma background is taken care of using the Debye screening model which admits of a wide variety of plasma conditions. Transition energies as well as the analytical wave functions of the doubly excited states have been obtained from a study of the pole positions of the collective oscillation modes in the two‐electron charge cloud under a time‐dependent harmonic perturbation. The response properties of the system are analyzed from the linearized version of a suitably constructed variational functional. Most of the calculated data are new. Our results agree well with the relatively few existing experimental and theoretical data for the free ions. The general trend of the results show systematic behavior with respect to increased plasma strength, and the data may be useful from the astrophysical viewpoint. The doubly excited state wave functions have been used to calculate the Coulomb repulsion integrals to check their consistency and may be useful for evaluating other physical properties connected with transitions and also estimating the rate coefficients for dielectronic recombination processes, which play a major role in the diagnostic determination of high‐temperature plasmas. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005 [ABSTRACT FROM AUTHOR]

The article presents information about the 13 International Congress of the European Association for Endoscopic Surgery and Other Interventional Techniques and its joint meeting with International Pediatric Endosurgery Group that will be held from June 1-4, 2005 in Venice Lido, Italy. The general theme of the conference is New Trends in General and Oncologic Surgery from Venice. Located on the Lungomare, the Conference Center is easily accessible from San Marco square and from the Marco Polo International Airport across the Venice Lagoon.