Vesico-urethral anastomotic stenosis following radical prostatectomy: a multi-institutional outcome analysis with a focus on endoscopic approach, surgical sequence, and the impact of radiation therapy.

OBJECTIVES: To investigate the predictors of recurrence and of de novo incontinence in patients treated by transurethral incision or resection for vesico-urethral anastomotic stenosis (VUAS) after radical prostatectomy. MATERIAL AND METHODS: All patients undergoing endoscopic treatment for VUAS between March 2009 and October 2016 were identified in our multi-institutional database. Digital chart reviews were performed and patients contacted for follow-up. Recurrence was defined as any need for further instrumentation or surgery, and de-novo-incontinence as patient-reported outcome. RESULTS: Of 103 patients undergoing endoscopic VUAS treatment, 67 (65%) underwent transurethral resection (TR) and 36 (35%) transurethral incision (TI). TI was performed more frequently as primary treatment compared to TR (58% vs. 37%; p = 0.041). Primary and repeated treatment was performed in 46 (45%) and 57 patients (55%), respectively. Overall, 38 patients (37%) had a history of radiation therapy. There was no difference in time to recurrence for primary vs repeat VUAS treatment, previous vs no radiation, TR compared to TI (all p > 0.08). Regarding treatment success, no difference was found for primary vs. repeat VUAS treatment (50% vs. 37%), previous radiation vs. no radiation (42% vs. 43%), and TR vs. TI (37% vs. 53%; all p ≥ 0.1). Postoperative de novo incontinence was more common after TI vs. TR (31% vs. 12%; p = 0.032), no difference was observed for previous radiation therapy vs. no radiation therapy (18% vs. 18%; p > 0.9) or primary vs. repeat VUAS treatment (22% vs. 16%; p = 0.5). CONCLUSION: VUAS recurrence after endoscopic treatment is not predictable. Endoscopic treatment with TI showed a higher risk for de novo incontinence than TR, and previous irradiation and the number of treatments do not influence incontinence.

Efficacy of anti-programmed cell death-1 immunotherapy for skin carcinomas and melanoma metastases in a patient with xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is an orphan disease of poor prognosis. We report one case of parallel efficacy with anti-programmed cell death-1 (PD-1) antibody on both melanoma and skin carcinoma in a patient with XP. A 17-year-old patient presented with metastatic melanoma and multiple nonmelanoma skin cancers. He was treated with pembrolizumab, a monoclonal anti-PD-1 antibody, at a dose of 2 mg kg-1 , every 3 weeks. Parallel therapeutic efficacy of anti-PD-1 was observed in metastatic melanoma and skin carcinomas, and maintained at week 24. This observation suggests anti-PD-1 may be considered in patients with XP and metastatic melanoma in addition to advanced nonmelanoma skin cancer.

Challenges of DHS and MIS to capture the entire pattern of malaria parasite risk and intervention effects in countries with different ecological zones: the case of Cameroon.

BACKGROUND: In 2011, the demographic and health survey (DHS) in Cameroon was combined with the multiple indicator cluster survey. Malaria parasitological data were collected, but the survey period did not overlap with the high malaria transmission season. A malaria indicator survey (MIS) was also conducted during the same year, within the malaria peak transmission season. This study compares estimates of the geographical distribution of malaria parasite risk and of the effects of interventions obtained from the DHS and MIS survey data. METHODS: Bayesian geostatistical models were applied on DHS and MIS data to obtain georeferenced estimates of the malaria parasite prevalence and to assess the effects of interventions. Climatic predictors were retrieved from satellite sources. Geostatistical variable selection was used to identify the most important climatic predictors and indicators of malaria interventions. RESULTS: The overall observed malaria parasite risk among children was 33 and 30% in the DHS and MIS data, respectively. Both datasets identified the Normalized Difference Vegetation Index and the altitude as important predictors of the geographical distribution of the disease. However, MIS selected additional climatic factors as important disease predictors. The magnitude of the estimated malaria parasite risk at national level was similar in both surveys. Nevertheless, DHS estimates lower risk in the North and Coastal areas. MIS did not find any important intervention effects, although DHS revealed that the proportion of population with an insecticide-treated nets access in their household was statistically important. An important negative relationship between malaria parasitaemia and socioeconomic factors, such as the level of mother's education, place of residence and the household welfare were captured by both surveys. CONCLUSION: Timing of the malaria survey influences estimates of the geographical distribution of disease risk, especially in settings with seasonal transmission. In countries with different ecological zones and thus different seasonal patterns, a single survey may not be able to identify all high risk areas. A continuous MIS or a combination of MIS, health information system data and data from sentinel sites may be able to capture the disease risk distribution in space across different seasons.

Why we should not routinely apply irreversible electroporation as an alternative curative treatment modality for localized prostate cancer at this stage.

Irreversible electroporation (IRE), a new tissue ablation procedure available since 2007, could meet the requirements for ideal focal therapy of prostate cancer with its postulated features, especially the absence of a thermal ablation effect. Thus far, there is not enough evidence of its effectiveness or adverse effects to justify its use as a definitive treatment option for localized prostate cancer. Moreover, neither optimal nor individual treatment parameters nor uniform endpoints have been defined thus far. No advantages over established treatment procedures have as yet been demonstrated. Nevertheless, IRE is now being increasingly applied for primary prostate cancer therapy outside clinical trials, not least through active advertising in the lay press. This review reflects the previous relevant literature on IRE of the prostate or prostate cancer and shows why we should not adopt IRE as a routine treatment modality at this stage.

Utilization of multiparametric prostate magnetic resonance imaging in clinical practice and focal therapy: report from a Delphi consensus project.

PURPOSE: To codify the use of multiparametric magnetic resonance imaging (mpMRI) for the interrogation of prostate neoplasia (PCa) in clinical practice and focal therapy (FT). METHODS: An international collaborative consensus project was undertaken using the Delphi method among experts in the field of PCa. An online questionnaire was presented in three consecutive rounds and modified each round based on the comments provided by the experts. Subsequently, a face-to-face meeting was held to discuss and finalize the consensus results. RESULTS: mpMRI should be performed in patients with prior negative biopsies if clinical suspicion remains, but not instead of the PSA test, nor as a stand-alone diagnostic tool or mpMRI-targeted biopsies only. It is not recommended to use a 1.5 Tesla MRI scanner without an endorectal or pelvic phased-array coil. mpMRI should be performed following standard biopsy-based PCa diagnosis in both the planning and follow-up of FT. If a lesion is seen, MRI-TRUS fusion biopsies should be performed for FT planning. Systematic biopsies are still required for FT planning in biopsy-naïve patients and for patients with residual PCa after FT. Standard repeat biopsies should be taken during the follow-up of FT. The final decision to perform FT should be based on histopathology. However, these consensus statements may differ for expert centers versus non-expert centers. CONCLUSIONS: The mpMRI is an important tool for characterizing and targeting PCa in clinical practice and FT. Standardization of acquisition and reading should be the main priority to guarantee consistent mpMRI quality throughout the urological community.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project.

PURPOSE: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). METHODS: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. RESULTS: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. CONCLUSION: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

No impact of blood transfusion on oncological outcome after radical prostatectomy in patients with prostate cancer.

PURPOSE: To assess the association between blood loss, blood transfusion (BT) and biochemical recurrence (BCR)-free, metastasis-free and overall survival after radical prostatectomy (RP) in a large single-center cohort of patients. Perioperative BT at oncologic surgery has been reported to be a potential risk factor for cancer recurrence and survival in several cancer entities. Current studies addressing the relationship between BT, blood loss and BCR-free survival in prostate cancer patients are controversial and include only series with fairly small patient cohorts. MATERIALS AND METHODS: The data of 11,723 patients who underwent RP between 01/1992 and 08/2011 were analyzed. Cox regression analysis, including preoperative PSA level, pT stage, lymph node status, Gleason score, margin status, blood loss, transfusion rate (allogeneic or autologous), tested the relationship between blood loss, transfusion and BCR-free, metastasis-free and overall survival. Additionally, propensity score-matching analysis was performed to adjust differences in tumor characteristics. RESULTS: There was no statistically significant relationship between blood loss or BT and BCR-free, metastasis-free or overall survival. In multivariate analysis PSA level, pT stage, Gleason score, margin status and lymph node status were independent factors for a BCR (p < 0.0001). These results were identical after propensity score matching analysis, comparing patients with and without BT. CONCLUSIONS: This large-scale analysis revealed no correlation between blood loss, blood transfusion and oncological outcome in prostate cancer patients treated with RP. Therefore, the association between higher blood loss or transfusion rate and cancer recurrence as described in other surgical treated tumor entities seems to be irrelevant in prostate cancer patients.

Comparison of prostate cancer volume measured by HistoScanning™ and final histopathological results.

PURPOSE: HistoScanning™ (HS) is an ultrasound-based tissue characterization technique with encouraging results in the detection of prostate cancer (PCa). The aim of this study was to evaluate the accuracy of total tumor volume measured by HS (TVHS) in patients with PCa. METHODS: In 148 patients with proven PCa, TVHS was measured prior to radical prostatectomy and compared with the total tumor volume in the final pathological report (TVP) using the rank-based spearman correlation test. Correlation was performed after stratification of the results by d'Amico risk categories, prostate volume, experience of HS examiner, distance of the ultrasound probe to the prostate (≤3.5 and >3.5 mm) and quality of initial HS. In addition, a re-analysis of HS data was performed by a single examiner and the TVHS from the unmodified HS data was acquired. RESULTS: TVP was approximately twofold higher compared to TVHS. Overall, there was no significant correlation (r s = -0.0083, p = 0.9) for the TVP and the TVHS. After adjusting for d'Amico risk categories, prostate volume, experience of examiner, distance of the ultrasound probe to the prostate and quality of initial HS, no significant correlation was found. After re-analyzing of all HS data by 1 examiner, the correlation remained not significant (r s = 0.039, p = 0.6). CONCLUSIONS: TVHS and TVP did not correlate in this cohort of patients. We cannot recommend the use of HS at least for imaging of the total tumor volume at this time. The controversial findings for prostate HS should initiate more studies to clarify these discrepancies.

Does HistoScanning™ predict positive results in prostate biopsy? A retrospective analysis of 1,188 sextants of the prostate.

PURPOSE: The role of HistoScanning™ (HS) in prostate biopsy is still indeterminate. Existing literature is sparse and controversial. To provide more evidence according to that important clinical topic, we analyzed institutional data from the Martini-Clinic, Prostate Cancer Center, Hamburg. METHODS: Patients who received prostate biopsy and who also received HS were included in the study cohort. A single examiner, blinded to pathological results, re-analyzed all HS data in accordance with sextants of the prostate. Each sextant was considered as an individual case. Corresponding results from biopsy and HS were analyzed. The area under the receiver-operating characteristic curve (AUC) for the prediction of a positive biopsy by HS was calculated. Furthermore, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were assessed according to different HS signal volume cutoffs (>0, >0.2 and >0.5 ml). RESULTS: Overall, 198 men were identified and 1,188 sextants were analyzed. The AUC to predict positive biopsy results by HS was 0.58. Sensitivity, specificity, PPV and NPV for HS to predict positive biopsy results per sextant, depending on different HS signal volume cutoffs (>0, >0.2 and >0.5 ml) were 84.1, 27.7, 29.5 and 82.9 %, 60.9, 50.6, 28.8 and 79.7 %, and 40.1, 73.3, 33.1 and 78.8 %, respectively. CONCLUSIONS: Positive HS signals do not accurately predict positive prostate biopsy results according to sextant analysis. We cannot recommend a variation of well-established random biopsy patterns or reduction of biopsy cores in accordance with HS signals at the moment.

Blind Source Separation for Clutter and Noise Suppression in Ultrasound Imaging: Review for Different Applications.

Blind source separation (BSS) refers to a number of signal processing techniques that decompose a signal into several "source" signals. In recent years, BSS is increasingly employed for the suppression of clutter and noise in ultrasonic imaging. In particular, its ability to separate sources based on measures of independence rather than their temporal or spatial frequency content makes BSS a powerful filtering tool for data in which the desired and undesired signals overlap in the spectral domain. The purpose of this work was to review the existing BSS methods and their potential in ultrasound imaging. Furthermore, we tested and compared the effectiveness of these techniques in the field of contrast-ultrasound super-resolution, contrast quantification, and speckle tracking. For all applications, this was done in silico, in vitro, and in vivo. We found that the critical step in BSS filtering is the identification of components containing the desired signal and highlighted the value of a priori domain knowledge to define effective criteria for signal component selection.

Synthetic Elastography Using B-Mode Ultrasound Through a Deep Fully Convolutional Neural Network.

Shear-wave elastography (SWE) permits local estimation of tissue elasticity, an important imaging marker in biomedicine. This recently developed, advanced technique assesses the speed of a laterally traveling shear wave after an acoustic radiation force "push" to estimate local Young's moduli in an operator-independent fashion. In this work, we show how synthetic SWE (sSWE) images can be generated based on conventional B-mode imaging through deep learning. Using side-by-side-view B-mode/SWE images collected in 50 patients with prostate cancer, we show that sSWE images with a pixel-wise mean absolute error of 4.5 ± 0.96 kPa with regard to the original SWE can be generated. Visualization of high-level feature levels through t -distributed stochastic neighbor embedding reveals substantial overlap between data from two different scanners. Qualitatively, we examined the use of the sSWE methodology for B-mode images obtained with a scanner without SWE functionality. We also examined the use of this type of network in elasticity imaging in the thyroid. Limitations of the technique reside in the fact that networks have to be retrained for different organs, and that the method requires standardization of the imaging settings and procedure. Future research will be aimed at the development of sSWE as an elasticity-related tissue typing strategy that is solely based on B-mode ultrasound acquisition, and the examination of its clinical utility.

Intermediate filaments in nervous tissues.

Intermediate filaments have been isolated from rabbit intradural spinal nerve roots by the axonal flotation method. This method was modified to avoid exposure of axons to low ionic strength medium. The purified filaments are morphologically 75-80 percent pure. The gel electrophoretogram shows four major bands migrating at 200,000, 145,000, 68,000, and 60,000 daltons, respectively. A similar preparation from rabbit brain shows four major polypeptides with mol wt of 200,000 145,000, 68,000, and 51,000 daltons. These results indicate that the neurofilament is composed of a triplet of polypepetides with mol wt of 200,000, 145,000, and 68,000 daltons. The 51,000-dalton band that appears in brain filament preparations as the major polypeptide seems to be of glial origin. The significance of the 60,000- dalton band in the nerve root filament preparation is unclear at this time. Antibodies raised against two of the triplet proteins isolated from calf brain localize by immunofluorescence to neurons in central and peripheral nerve. On the other hand, an antibody to the 51,000-dalton polypeptide gives only glial staining in the brain, and very weak peripheral nerve staining. Prolonged exposure of axons to low ionic strength medium solubilizes almost all of the triplet polypeptides, leaving behind only the 51,000- dalton component. This would indicate that the neurofilament is soluble at low ionic strength, whereas the glial filament is not. These results indicate that neurofilaments and glial filaments are composed of different polypeptides and have different solubility characteristics.

[Imaging for initial diagnosis of localized prostate cancer]. / Bildgebung im Rahmen der Primärdiagnostik beim lokal begrenzten Prostatakarzinom.

The initial diagnosis of prostate cancer has been traditionally performed using systematic core biopsies with the use of magnetic resonance imaging (MRI) reserved to problem-solving scenarios. There is currently an ongoing paradigm shift towards the use of MRI prior to targeted biopsy as the standard approach. Prostate cancer therefore does not remain the last solid tumor entity diagnosed by non-targeted techniques but joins other solid tumor entities for which targeted diagnostic approaches have existed for a while. However, the complexity of the background tissue signal in the prostate makes lesion detection challenging. This article will provide an overview of the components of multiparametric prostate MRI and their interpretation using structured interpretation according to the current PI-RADSv2 (Prostate Imaging Reporting and Data System version 2) guidelines and of novel ultrasound techniques for primary diagnosis.

[The role of the vesical imaging-reporting and data system (VI-RADS) for bladder cancer diagnostics-status quo]. / Bedeutung der VI-RADS-Klassifikation für die Bildgebung beim Harnblasenkarzinom ­ Stand der Dinge.

Initial clinical and pathological diagnostic workup of urinary bladder cancer is based on cystoscopy, transurethral resection of suspicious lesions, and computed tomography when indicated. Accurate staging is necessary for further therapeutic decision-making. This review summarizes the current status of multiparametric magnetic resonance imaging (mpMRI) and the vesical imaging-reporting and data system (VI-RADS) classification. MpMRI may improve the accuracy of assessment of local tumor invasion compared to conventional imaging alone. VI-RADS standardizes reporting of MRI staging and classifies the likelihood of muscle-invasive bladder cancer into five categories. Preliminary data suggest low interobserver variability. However, prospective multicenter studies are necessary to validate the VI-RADS classification. Progress in functional, molecular, and hybrid imaging may further improve the accuracy of clinical tumor and nodal staging for bladder cancer.

[PSA increase after definitive treatment]. / PSA-Anstieg nach definitiver Therapie.

Following definitive treatment with curative intent a subset of patients with prostate cancer experience biochemical recurrence. In these patients clinical parameters are mostly used to decide if a local or systemic disease recurrence is present. While salvage radiation treatment is advocated for local recurrence after radical prostatectomy, no standard recommendations exist in cases of local recurrence after primary radiation therapy although salvage prostatectomy may be considered. Imaging procedures have traditionally not routinely been recommended for the onset of prostate-specific antigen (PSA) relapse; however, prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computed tomography (CT) exhibits high detection rates even at low PSA values. Thus, the current German guidelines state that PSMA PET/CT can be considered if this could result in a decisive change in further treatment management. Currently, a positive influence on oncological long-term outcome, however, has not yet been proven.

[Active surveillance for prostate cancer]. / Aktive Uberwachung des Prostatakarzinoms.

Active surveillance is a valuable treatment option in patients with newly diagnosed low-risk prostate cancer. Studies considering a watchful waiting approach showed favourable cancer-specific survival rates in such patients and it is assumed that patients benefit from a definitive therapy if life expectancy exceeds 10-15 years. Therefore active surveillance is especially valuable in older men and in patients with an elevated comorbidity profile. Precise identification of histologically and clinically insignificant prostate cancers is still not possible today. Active surveillance includes regular PSA measurements combined with follow-up biopsies; however, no standardized protocol exists so far. Histological progression in the follow-up biopsy and PSA elevation are the most important criteria for initiating definitive therapy. Today only a minority of low-risk patients join an active surveillance protocol and a substantial proportion of these men leave such a protocol early without evidence of progression. The psychological burden of living with an untreated cancer seems to be responsible for this. Active surveillance has the potential to lead to undertreatment as there is some evidence that prolonged treatment delay might adversely affect outcome of definitive therapy.

[Focal therapy of prostate cancer]. / Fokale Therapie des Prostatakarzinoms.

The target of focal therapy (FT) in prostate cancer (PC) is partial treatment of the prostate aiming at preserving surrounding anatomical structures. The intention is to minimize typical side effects of radical treatment options combined with local tumor control. Numerous established and new technologies are used. Results of published studies showed a good safety profile, few side effects and good preservation of functional results. Oncologic long-term data are lacking so far. Photodynamic therapy (PDT) is the only technology that has been studied in a published prospective randomized trial. The FT is challenged by the multifocality of PC; therefore, the quality of prostate biopsy, histopathological assessment as well as imaging are of paramount importance. Multiparametric magnetic resonance imaging (MRI) has gained increasing importance. The FT is experimental and should only be offered within clinical trials.