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To compare oncological and functional outcomes of high-intensity focused-ultrasound (HIFU) focal therapy (FT) versus laparoscopic radical prostatectomy (LRP) in patients treated for low- or intermediate-risk prostate cancer (PCa), we retrospectively analyzed data of consecutive patients comprising 30 men, who underwent HIFU-FT, and 96 men who underwent LRP, in an academic center. Oncological outcomes were assessed based on the follow-up prostate-specific antigen values. We used the International Index of Erectile Function short form score to assess erectile function (EF). Urinary continence status was defined based on the number of pads used per day. Median follow-up was 12.5 and 19.1 months in the LRP and HIFU-FT groups, respectively. The effects were computed after propensity score matching and expressed as average treatment effect (ATE). Compared to LRP, HIFU-FT was associated with increased risk of treatment failure (ATE 0.103–0.164, depending on definition, p < 0.01) and lower risk of urinary incontinence (ATE −0.808 at 12 months, p < 0.01). Risk of erectile dysfunction was higher in the LRP group (ATE 5.092, p < 0.01). Our results demonstrate that HIFU-FT may be a reasonable treatment option in selected PCa patients, willing to preserve their EF and urinary continence yet accepting a higher risk of treatment failure.

We have developed ComplexBrowser, an open source, online platform for supervised analysis of quantitative proteomic data (label free and isobaric mass tag based) that focuses on protein complexes. The software uses manually curated information from CORUM and Complex Portal databases to identify protein complex components. For the first time, we provide a Complex Fold Change (CFC) factor that identifies up- and down-regulated complexes based on the level of complex subunits co-regulation. The software provides interactive visualisation of protein complexes' composition and expression for exploratory analysis and incorporates a quality control step that includes normalisation and statistical analysis based on the limma package. ComplexBrowser was tested on two published studies identifying changes in protein expression within either human adenocarcinoma tissue or activated mouse T-cells. The analysis revealed 1,519 and 332 protein complexes, of which 233 and 41 were found co-ordinately regulated in the respective studies. The adopted approach provided evidence for a shift to glucose-based metabolism and high proliferation in adenocarcinoma tissues, and the identification of chromatin remodelling complexes involved in mouse T-cell activation. The results correlate with the original interpretation of the experiments and provide novel biological details about the protein complexes affected. ComplexBrowser is, to our knowledge, the first tool to automate quantitative protein complex analysis for high-throughput studies, providing insights into protein complex regulation within minutes of analysis.A fully functional demo version of ComplexBrowser is available online via http: //computproteomics.bmb.sdu.dk/Apps/ComplexBrowser/The source code can be downloaded from: https://bitbucket.org/michalakw/complexbrowser.

We have developed ComplexBrowser, an open source, online platform for supervised analysis of quantitative proteomics data that focuses on protein complexes. The software uses information from CORUM and Complex Portal databases to identify protein complex components. Based on the expression changes of individual complex subunits across the proteomics experiment it calculates Complex Fold Change (CFC) factor that characterises the overall protein complex expression trend and the level of subunit co-regulation. Thus up- and down-regulated complexes can be identified. It provides interactive visualisation of protein complexes composition and expression for exploratory analysis. It also incorporates a quality control step that includes normalisation and statistical analysis based on Limma test. ComplexBrowser performance was tested on two previously published proteomics studies identifying changes in protein expression in human adenocarcinoma tissue and during activation of mouse T-cells. The analysis revealed 1519 and 332 protein complexes, of which 233 and 41 were found co-ordinately regulated in the respective studies. The adopted approach provided evidence for a shift to glucose-based metabolism and high proliferation in adenocarcinoma tissues and identification of chromatin remodelling complexes involved in mouse T-cell activation. The results correlate with the original interpretation of the experiments and also provide novel biological details about protein complexes affected. ComplexBrowser is, to our knowledge, the first tool to automate quantitative protein complex analysis for high-throughput studies, providing insights into protein complex regulation within minutes of analysis.A fully functional demo version of ComplexBrowser v1.0 is available online via http://computproteomics.bmb.sdu.dk/Apps/ComplexBrowser/The source code can be downloaded from: https://bitbucket.org/michalakw/complexbrowserHighlightsAutomated analysis of protein complexes in proteomics experimentsQuantitative measure of the coordinated changes in protein complex componentsInteractive visualisations for exploratory analysis of proteomics resultsIn briefComplexBrowser is capable of identifying protein complexes in datasets obtained from large scale quantitative proteomics experiments. It provides, in the form of the CFC factor, a quantitative measure of the coordinated changes in complex components. This facilitates assessing the overall trends in the processes governed by the identified protein complexes providing a new and complementary way of interpreting proteomics experiments.

ContextMagnetic resonance imaging (MRI) is currently the most accurate imaging modality to assess local prostate cancer stage. Despite a growing body of evidence, incorporation of MRI images into decision-making process concerning surgical template of radical prostatectomy, is complex and still poorly understood.ObjectiveWe sought to determine the value of MRI in preoperative planning before radical prostatectomy.Materials and methodsSystematic search through electronic PubMed, EMBASE, and Cochrane databases from 2000 up to April 2018 was performed. Only studies that used preoperative MRI in decision-making process regarding extension of resection in patients with prostate cancer, in whom radical prostatectomy was an initial form of treatment were included into analysis. Their quality was scored by Risk Of Bias In Non-Randomized Studies of Interventions system. Meta-analysis was performed to calculate the weighted summary proportion under the fixed or random effects model as appropriate and pooled effects were depicted on forest plots.ResultsThe results showed that the preoperative MRI led to the modification of initial surgical template in one third of cases (35%). This occurred increasingly with the rising prostate cancer-risk category: 28%, 33%, 52% in low-, intermediate- and high-risk group, respectively. Modification of neurovascular bundle-sparing surgery based on MRI appeared to have no impact on the positive surgical margin rate. The decision based on MRI was correct on average in 77% of cases and differed across prostate cancer-risk categories: 63%, 75% and 91% in low-, intermediate- and high-risk group, accordingly.ConclusionsIn summary, MRI has a considerable impact on the decision-making process regarding the extent of resection during radical prostatectomy. Adaptation of MRI images by operating surgeons has at worst no significant impact on surgical margin status, however its ability to decrease the positive surgical margin rates remains unconfirmed.

Introduction We aimed to evaluate the diagnostic performance of 3.0-T multiparametric magnetic resonance imaging (mpMRI) in preoperative staging of prostate cancer (PCa) and its influence on the extent of resection during endoscopic radical prostatectomy (ERP) among cancer risk groups. Material and methods The data of 154 patients with PCa in whom mpMRI was performed prior to ERP between 2011 and 2015 were included. The initial decision whether to perform neurovascular bundle (NVB) sparing surgery was based on EAU guidelines. mpMRI images were reevaluated prior to prostatectomy to modify the surgical template. Imaging was compared with pathological reports to investigate the diagnostic performance of mpMRI. Results The surgical template was modified in 69 (44.8%) patients after reevaluation of mpMRI. More preserving NVB sparing was attempted in 17 (11.0%) men, in whom NVB would have been resected if mpMRI had not been available. More aggressive NVB resection was performed in 52 (33.8%) men, in whom innervation would have been spared if basing solely based on guidelines. Among all PCa risk groups mpMRI had an impact on the surgical template with more aggressive surgery in 63.0% and 33.3% of men in the low- and intermediate-risk group, respectively, and more preserving in 21.4% of the high-risk patients. The change in extent of resection was not correlated with a higher risk of positive surgical margins (p = 0.196). Conclusions Preoperative mpMRI exerts a significant impact on decision making concerning the extent of resection during ERP irrespective of the PCa risk group.

Objective: Recent years have brought a significant shift in case selection for the surgical treatment of prostate cancer (PCa). Primary surgical management is increasingly implemented in more aggressive tumors, however the role of radical prostatectomy (RP) in advanced cases remains controversial. The aim of the present study is to explore cancer diversity in patients who were subjected to endoscopic, transperitoneal RP due to very high-risk advanced PCa. Methods: Our database was screened for prostate cancer patients with clinically diagnosed seminal vesicles infiltration and/or invasion of other adjacent structures (cT3b-4 N0) and/or suspected nodal involvement (cT1-4 N1) who underwent ERP. Twenty cases were identified: 11 patients with cT3b-4 N0 disease and 9 patients with suspected nodal involvement. The preoperative tumor stage was assessed with the use of multiparametric magnetic resonance (mpMRI) in all cases. Results: Although the accuracy of mpMRI in the assessement of local tumor stage was 85%, the lymph node status was properly assessed preoperatively in 45% cases only. The pT3b-4 PCa was diagnosed in 13 cases (65%). Of them, 9 had lymph nodes metastases. Three patients (15%) were diagnosed with pT3a cancer, among them nodal metastases were confirmed in 2 cases. In the remaining 4 patients (20%), the tumor was confined to the prostate but in 1 of them pelvic lymph nodes were involved. Early, postoperative PSA was lower than 0.2 ng/ml in 13 patients (65%). Seventeen patients (85%) received additional treatment: androgen deprivation therapy in 7 cases (35%), radiation therapy in 10 cases (50%). No pad use was declared by 14 patients (70%). Conclusion: Radical prostatectomy thoroughly stratifies patients diagnosed with advanced prostate cancer. In more than a half of cases the clinical stage differs from the pathological disease status. Correct, postoperative prostate cancer stratification allows to personalize multidisciplinary treatment to reduce toxicity and improve oncological outcome.