A randomized trial investigating clinical outcomes and stent-related symptoms after placement of a complete intra-ureteric stent on a string versus conventional stent placement.

OBJECTIVE: To compare stent-related symptoms (SRS) associated with conventional ureteric JJ stent (CUS) placement and SRS associated with placement of a modified complete intra-ureteric stent (CIUS) with extraction suture, designed to minimize SRS, using the validated Ureteral Stent Symptom Questionnaire (USSQ). MATERIALS AND METHODS: We randomized 124 patients who had undergone uncomplicated ureteroscopic lithotripsy into a CIUS and a CUS placement group. USSQ scores were evaluated on postoperative days 1 and 7 (just before stent removal) and 4 weeks after stent removal (control values). Pain scores on a visual analogue scale (VAS) after stent removal were also recorded. Subdomain analysis of all SRS and stent-related complications were also compared. RESULTS: No significant intergroup differences were found in the domain scores for urinary symptoms (P = 0.74), pain (P = 0.32), general health (P = 0.27), work (P = 0.24), or additional problems (P = 0.29). However, a statistically significant difference was noted in VAS scores (P = 0.015). Analysis of subdomains of USSQ item scores showed the CIUS group had significantly better scores for urge incontinence (1.21 vs 1.00; P ≤ 0.001), discomfort on voiding (2.07 vs 1.50; P ≤ 0.001), difficulties with respect to light physical activity (1.131 vs 1.00; P ≤ 0.001), fatigue (1.84 vs 1.57; P = 0.002), feeling comfortable (3.68 vs 3.16; P = 0.003), need for extra help (1.96 vs 1.00; P ≤ 0.001), and change in duration of work (4.27 vs 1.86; P ≤ 0.001). However, the patients in the CIUS group were sexually inactive for the time during which the stent was indwelling (mean: 7.34 days). There was no difference in complication rates between the two groups. CONCLUSION: The use of a CIUS with strings after Ureteroscopy decreases SRS.

Super-mini percutaneous nephrolithotomy (PCNL) vs standard PCNL for the management of renal calculi of <2 cm: a randomised controlled study.

OBJECTIVE: To compare the effectiveness and safety of standard percutaneous nephrolithotomy (sPCNL) and super-mini PCNL (SMP). PATIENTS AND METHODS: A total of 150 patients presenting with renal calculi of <2 cm were randomised to either sPCNL (Group 1) or SMP (Group 2). Randomisation was based on centralised computer-generated numbers. Variables studied included: stone-free rates (SFRs), operative time, intra- and postoperative complications, postoperative pain score, analgesic requirement, and hospital stay. Statistical analysis was performed using a t-test or Mann-Whitney U-test for continuous variables and chi-squared test or Fisher's exact test for categorical variables. RESULTS: Between September 2018 and April 2019, 75 patients were included in each group. The SFRs of the groups were similar (97.33 vs 98.66%, P = 0.56). The mean (sd) operative time was significantly longer in Group 2, at 36.40 (14.07) vs 23.12 (11.96) min (P < 0.001). The mean (sd) decrease in haemoglobin was significantly less in Group 2, at 3.0 (4.9) vs 7.5 (6.5) g/L (P < 0.001). The mean (sd) pain score at 24 h was significantly lower in Group 2, at 0.3 (0.46) vs 0.75 (0.53) (P < 0.001). The mean (sd) analgesic requirement was significantly less in Group 2, at 67 (22.49) vs 91.5 (30.56) mg tramadol (P < 0.001). The mean (sd) hospital stay was significantly less in Group 2, at 28.38 (3.6) vs 39.84 (3.7) h (P < 0.001). CONCLUSIONS: SMP is equally as effective as sPCNL for managing renal calculi of <2 cm, with improved safety. Although SMP is associated with a longer operative time, it has a significantly lower incidence of bleeding and postoperative pain, and a shorter hospital stay.

Pre-Use Ureteroscope Contamination after High Level Disinfection: Reprocessing Effectiveness and the Relation with Cumulative Ureteroscope Use.

PURPOSE: We assessed the frequency of preoperative and persistent microbial contamination of flexible ureteroscopes after reprocessing and the relation of contamination to cumulative ureteroscope use. MATERIALS AND METHODS: We evaluated the effectiveness of high level disinfection with peracetic acid as well as data on ureteroscope use for 20 new flexible ureteroscopes from December 2015 to December 2017 at a single center. In the operating room pre-use and postuse microbial samples of the ureteroscope shaft and working channel were collected to evaluate microbial contamination after reprocessing. Positive cultures were defined as 30 cfu/ml or greater of skin flora, or 10 cfu/ml or greater of uropathogenic microorganisms. A generalized estimating equation model was used to analyze whether cumulative ureteroscope use was associated with positive pre-use cultures. RESULTS: Microbial samples were collected during 389 procedures. Pre-use ureteroscope cultures were positive in 47 of 389 procedures (12.1%), of which uropathogens were found in 9 of 389 (2.3%) and skin flora in 38 of 389 (9.8%). Urinary tract infection symptoms did not develop in any of the patients who underwent surgery with a uropathogen contaminated ureteroscope. In 1 case the pre-use culture contained the same bacteria type as the prior postuse culture. Cumulative ureteroscope use was not associated with a higher probability of positive cultures. CONCLUSIONS: Microbial contamination of reprocessed ureteroscopes was found in an eighth of all procedures. Notably uropathogenic microorganisms were discovered in a small proportion of all procedures. Persistent ureteroscope contamination with uropathogens was only rarely encountered. Cumulative ureteroscope use was not associated with a higher probability of microbial contamination.

Systematic review and cumulative analysis of the managements for proximal impacted ureteral stones.

PURPOSE: To compare the efficacy and safety of different treatment options for the management of proximal impacted ureteral stones (PIUS). METHODS: A systematic literature search using Pubmed, Medline, Embase and Cochrane Library was conducted to obtain studies concerning different managements for PIUS up to Jan 2018. Summary odds ratios (ORs), standard mean differences (SMDs) or weighted mean differences with their 95% confidence intervals (CIs) were calculated to compare the efficacy and safety of all included treatment methods, registered in PROSPERO under number CRD42018092745. RESULTS: A total of 15 comparative studies with 1780 patients were included. Meta-analyses of final stone-free rate (SFR) favored percutaneous nephrolithotomy (PCNL) over ureteroscopic lithotripsy (URL) (OR 10.35; 95% CI 5.26-20.35; P < 0.00001), laparoscopic ureterolithotomy over URL (OR 0.11; 95% CI 0.05-0.25; P < 0.00001) and URL over extracorporeal shockwave lithotripsy (OR 0.47; 95% CI 0.28-0.77; P = 0.003). As to complications, PCNL had a significantly higher blood transfusion rate (OR 7.47; 95% CI 1.3-42.85; P = 0.02) and a lower ureteral injury rate (OR 0.15; 95% CI 0.04-0.52; P = 0.003) compared with URL. It also shared a significantly lower stone-retropulsion rate (OR 0.03; 95% CI 0.01-0.15; P < 0.0001) and higher treatment costs (SMD = 2.71; 95% CI 0.71-4.70; P = 0.008) than URL. CONCLUSIONS: Our meta-analysis suggested that PCNL might be the best option for PIUS owing to its higher successful rate. Complications such as hemorrhage could be decreased by the application on mini-PCNL.

Analogous detection of circulating tumor cells using the AccuCyte® -CyteFinder® system and ISET system in patients with locally advanced and metastatic prostate cancer.

INTRODUCTION: Circulating tumor cells (CTCs) can provide important information on patient's prognosis and treatment efficacy. Currently, a plethora of methods is available for the detection of these rare cells. We compared the outcomes of two of those methods to enumerate and characterize CTCs in patients with locally advanced and metastatic prostate cancer (PCa). First, the selection-free AccuCyte® - CyteFinder® system (RareCyte® , Inc., Seattle, WA) and second, the ISET system (Rarecells Diagnostics, France), a CTC detection method based on cell size-exclusion. METHODS: Peripheral blood samples were obtained from 15 patients with metastatic PCa and processed in parallel, using both methods according to manufacturer's protocol. CTCs were identified by immunofluorescence, using commercially available antibodies to pancytokeratin (PanCK), EpCAM, CD45/CD66b/CD34/CD11b/CD14 (AccuCyte® - CyteFinder® system), and pancytokeratin, vimentin (Vim) and CD45 (ISET system). RESULTS: The median CTC count was 5 CTCs/7.5 mL (range, 0-20) for the AccuCyte® - CyteFinder® system and 37 CTCs/7.5 mL (range, 8-139) for the ISET system (P < 0.001). Total CTC counts obtained for the two methods were correlated (r = 0.750, P = 0.001). When separating the total CTC count obtained with the ISET system in PanCK+/Vim- and PanCK+/Vim+ CTCs, the total CTC count obtained with the AccuCyte® - CyteFinder® system was moderately correlated with the PanCK+/Vim- CTCs, and strongly correlated with the PanCK+/Vim+ CTCs (r = 0.700, P = 0.004 and r = 0.810, P < 0.001, respectively). CONCLUSION: Our results highlight significant disparities in the enumeration and phenotype of CTCs detected by both techniques. Although the median amount of CTCs/7.5 mL differed significantly, total CTC counts of both methods were strongly correlated. For future studies, a more uniform approach to the isolation and definition of CTCs based on immunofluorescent stains is needed to provide reproducible results that can be correlated with clinical outcomes.

An In-Depth Glycosylation Assay for Urinary Prostate-Specific Antigen.

The concentration of prostate-specific antigen (PSA) in serum is used as an early detection method of prostate cancer (PCa); however, it shows low sensitivity, specificity, and a poor predictive value. Initial studies suggested the glycosylation of PSA to be a promising marker for a more specific yet noninvasive PCa diagnosis. Recent studies on the molecular features of PSA glycosylation (such as antenna modification and core fucosylation) were not successful in demonstrating its potential for an improved PCa diagnosis, probably due to the lack of analytical sensitivity and specificity of the applied assays. In this study, we established for the first time a high-performance PSA Glycomics Assay (PGA), allowing differentiation of α2,6- and α2,3-sialylated isomers, the latter one being suggested to be a hallmark of aggressive types of cancer. After affinity purification from urine and tryptic digestion, PSA samples were analyzed by CE-ESI-MS (capillary electrophoresis-electrospray ionization coupled to mass spectrometry). Based on positive controls, an average interday relative standard deviation of 14% for 41 N-glycopeptides was found. The assay was further verified by analyzing PSA captured from patients' urine samples. A total of 67 N-glycopeptides were identified from the PSA pooled from the patients. In summary, the first PGA successfully established in this study allows an in-depth relative quantitation of PSA glycoforms from urine. The PGA is a promising tool for the determination of potential glycomic biomarkers for the differentiation between aggressive PCa, indolent PCa, and benign prostate hyperplasia in larger cohort studies.

Super-mini percutaneous nephrolithotomy (SMP) vs retrograde intrarenal surgery for the treatment of 1-2 cm lower-pole renal calculi: an international multicentre randomised controlled trial.

OBJECTIVES: To compare the safety and effectiveness of super-mini-percutaneous nephrolithotomy (SMP) and retrograde intrarenal surgery (RIRS) for the treatment of 1-2 cm lower-pole renal calculi (LPC). PATIENTS AND METHODS: An international multicentre, prospective, randomised, unblinded controlled study was conducted at 10 academic medical centres in China, India, and Turkey, between August 2015 and June 2017. In all, 160 consecutive patients with 1-2 cm LPC were randomised to receive SMP or RIRS. The primary endpoint was stone-free rate (SFR). Stone-free status was defined as no residual fragments of ≥0.3 cm on plain abdominal radiograph of the kidneys, ureters and bladder, and ultrasonography at 1-day and on computed tomography at 3-months after operation. Secondary endpoints included blood loss, operating time, postoperative pain scores, auxiliary procedures, complications, and hospital stay. Postoperative follow-up was scheduled at 3 months. Analysis was by intention-to-treat. The trial was registered at http://clinicaltrials.gov/ (NCT02519634). RESULTS: The two groups had similar baseline characteristics. The mean (sd) stone diameters were comparable between the groups, at 1.50 (0.29) cm for the SMP group vs 1.43 (0.34) cm for the RIRS group (P = 0.214). SMP achieved a significantly better 1-day and 3-month SFR than RIRS (1-day SFR 91.2% vs 71.2%, P = 0.001; 3-months SFR 93.8% vs 82.5%, P = 0.028). The auxiliary procedure rate was lower in the SMP group. RIRS was found to be superior with lower haemoglobin drop and less postoperative pain. Blood transfusion was not required in either group. There was no significant difference in operating time, hospital stay, and complication rates, between the groups. CONCLUSIONS: SMP was more effective than RIRS for treating 1-2 cm LPC in terms of a better SFR and lesser auxiliary procedure rate. The complications and hospital stay were comparable. RIRS has the advantage of less postoperative pain.

Surgical teaching in urology: patient safety and educational value of 'LIVE' and 'SEMI-LIVE' surgical demonstrations.

PURPOSE: To evaluate the opinion of urologists and their audience regarding patient safety and educational value of live surgical demonstrations (LSD) and semi-live surgical demonstrations (semi-LSD). METHODS: Following the '2017 Challenges in Endourology' meeting, a survey addressing patient safety and the educational value of LSD and semi-LSD was disseminated online to all participants. Survey outcomes of LSD and semi-LSD were compared. RESULTS: All 279 respondents attended both LSD and semi-LSD. Overall, 53% of said respondents stated that patient safety was always the highest priority for LSD, while 74% noted the same for semi-LSD. The complication risk in LSD was perceived equal by 57% of the respondents when compared to cases of similar difficulty in routine practice, while 38% perceived it as a greater risk. For semi-LSD, the complication risk was perceived equal by 84%, while 5% perceived it to be a greater risk in comparison to general practice. On a scale from 0 (no value) to 10 (highly valuable), the average educational value of LSD and semi-LSD was rated 8.4 and 8.3, respectively. A substantial percentage of the surgeons who perform LSD express concerns that live surgery is not the optimal setting to ensure patient safety. CONCLUSIONS: LSD remains a popular tool for surgical education among urologists and their audience. However, patient safety remains a concern and is perceived less of a concern for semi-LSD. The educational value of LSD and semi-LSD was scored equally high. Therefore, we should consider to advocate the use of semi-LSD more often.

Pair-matched patient-reported quality of life and early oncological control following focal irreversible electroporation versus robot-assisted radical prostatectomy.

PURPOSE: The design, conduct and completion of randomized trials for curative prostate cancer (PCa) treatments are challenging. To evaluate the effect of robot-assisted radical prostatectomy (RARP) versus focal irreversible electroporation (IRE) on patient-reported quality of life (QoL) and early oncological control using propensity-scored matching. METHODS: Patients with T1c-cT2b significant PCa (high-volume ISUP 1 or any 2/3) who received unifocal IRE were pair-matched to patients who received nerve-sparing RARP. Patient-reported outcomes were prospectively assessed using the Expanded Prostate Cancer Index Composite (EPIC), AUA symptom score and Short Form of Health Survey (SF-12) physical and mental components. Oncological failure was defined as biochemical recurrence (RARP) or positive follow-up biopsies (IRE). Generalized mixed-effect models were used to compare IRE and RARP. RESULTS: 50 IRE patients were matched to 50 RARP patients by propensity score. IRE was significantly superior to RARP in preserving pad-free continence (UC) and erections sufficient for intercourse (ESI). The absolute differences were 44, 21, 13, 14% for UC and 32, 46, 27, 22% for ESI at 1.5, 3, 6, and 12 months, respectively. The EPIC summary scores showed no statistically significant differences. Urinary symptoms were reduced for IRE and RARP patients at 12 months, although IRE patient initially had more complaints. IRE patients experienced more early oncological failure than RARP patients. CONCLUSIONS: These data demonstrated the superior preservation of UC and ESI with IRE compared to RARP up to 12 months after treatment. Long-term oncological data are warranted to provide ultimate proof for or against focal therapy.

Same Session Bilateral Ureteroscopy for Multiple Stones: Results from the CROES URS Global Study.

PURPOSE: This study presents a comparison of the international experience with ipsilateral and bilateral ureteroscopy for multiple, bilateral ureteral and renal stones vs single stone treatment. Patient and treatment characteristics and outcomes were compared. MATERIALS AND METHODS: The CROES (Clinical Research Office of the Endourological Society) Ureteroscopy Global Study includes 114 centers in 32 countries. Patients undergoing bilateral ureteroscopy, ipsilateral ureteroscopy for multiple stones and ureteroscopy for a single stone were examined from January 2010 to October 2012. Intraoperative characteristics and postoperative outcomes were identified for each patient. Inverse probability weighted regression adjustment analyses were done to compare outcomes independent of differences among centers and patient characteristics. RESULTS: The CROES Ureteroscopy Global Study consists of 11,885 patients. A total of 2,153 patients (18.7%) were treated for multiple stones, of whom 1,880 (87.3%) and 273 (12.7%) underwent ipsilateral and bilateral ureteroscopy, respectively. Inverse probability weighted regression adjustment models for bilateral vs ipsilateral ureteroscopy and multiple vs single stone treatments showed that patients with bilateral ureteroscopy and multiple stone treatments had lower stone-free rates, higher re-treatment rates and longer operative times compared to patients who underwent ipsilateral ureteroscopy and single stone treatment. There was no difference in complication rates among bilateral, ipsilateral and single stone ureteroscopy. CONCLUSIONS: This study presents a large series of patients who underwent bilateral and ipsilateral ureteroscopy. Our findings suggest a decrease in stone-free rates, increased re-treatment rates, increased operative times and longer hospital stay in patients treated for multiple stones. The treatment of multiple stones and bilateral ureteroscopy are safe compared to single stone treatment and ipsilateral ureteroscopy, respectively.

Characteristics and outcomes of ureteroscopic treatment in 2650 patients with impacted ureteral stones.

PURPOSE: To describe stone-free rates and complications of ureteroscopic treatment for impacted compared with non-impacted ureteral stones and evaluate predictive variables for impaction. METHODS: The Clinical Research Office of the Endourological Society prospectively collected 1 consecutive year of data from 114 centers worldwide. Patients eligible for inclusion were patients treated with ureteroscopy for ureteral stones. Patient characteristics, treatment details, and outcomes were compared with regard to stone impaction. Logistic regression analyses were conducted to explore predictive variables for ureteral stone impaction and to analyse the effect of impaction on outcomes. RESULTS: Of the 8543 treated patients, 2650 (31%) had impacted and 5893 (69%) non-impacted stones. The stone-free rate was 87.1% for impacted stones, which is lower compared with 92.7% for non-impacted stones (p < 0.001). Intra-operative complication rates were higher for impacted stones (7.9 versus 3.0%, p < 0.001). Significantly higher ureteral perforation- and avulsion rates were reported in the impacted stone group compared with the non-impacted stone group. No association between stone impaction and post-operative complications could be shown. Female gender, ASA-score >1, prior stone treatment, positive pre-operative urine culture, and larger stones showed to be predictive variables for stone impaction. CONCLUSIONS: Ureteroscopic treatment for impacted stones is associated with lower stone-free rates and higher intra-operative complication rates compared with treatment for non-impacted stones. The predictive variables for the presence of stone impaction may contribute to the identification of stone impaction during the diagnostic process. Moreover, identification of stone impaction may aid the selection of the optimal treatment modality.

New technologies for upper tract urothelial carcinoma management.

PURPOSE OF REVIEW: Image enhancement techniques and optical diagnostic tools have emerged in the quest to improve diagnostics and treatment in patients with upper urinary tract carcinoma (UTUC). The aim of the present report is to describe their mechanisms of action and to assess the current evidence on applicability and utility in UTUC. RECENT FINDINGS: Image enhancement techniques including narrow band imaging, Image1 S, and photodynamic diagnosis aim at better visualization of malignant urothelium and especially flat tumours or carcinoma in situ which are often difficult to see with white light endoscopy. Conducted studies in the upper tract are scarce but first results show that tumour detection seems to be better for narrow band imaging and photodynamic diagnosis-guided inspection.Optical diagnostic tools as confocal laser endomicroscopy and optical coherence tomography aim at providing real time optical biopsies giving pathologic information. A pilot study of optical coherence tomography proved its feasibility to visualize, grade and stage low and high-grade UTUC. SUMMARY: Better visualization of suspect lesions and optical diagnostic techniques providing real time optical biopsies aim to facilitate in higher diagnostic precision and optimal individualized treatment of our patients with UTUC. As the disease is rare, studies are scarce but indispensable for future implication of these techniques.

Percutaneous Needle Based Optical Coherence Tomography for the Differentiation of Renal Masses: a Pilot Cohort.

PURPOSE: We determine the ability of percutaneous needle based optical coherence tomography to differentiate renal masses by using the attenuation coefficient (µOCT, mm(-1)) as a quantitative measure. MATERIALS AND METHODS: Percutaneous needle based optical coherence tomography of the kidney was performed in patients presenting with a solid renal mass. A pathology specimen was acquired in the form of biopsies and/or a resection specimen. Optical coherence tomography results of 40 patients were correlated to pathology results of the resected specimens in order to derive µOCT values corresponding with oncocytoma and renal cell carcinoma, and with the 3 main subgroups of renal cell carcinoma. The sensitivity and specificity of optical coherence tomography in differentiating between oncocytoma and renal cell carcinoma were assessed through ROC analysis. RESULTS: The median µOCT of oncocytoma (3.38 mm(-1)) was significantly lower (p=0.043) than the median µOCT of renal cell carcinoma (4.37 mm(-1)). ROC analysis showed a µOCT cutoff value of greater than 3.8 mm(-1) to yield a sensitivity, specificity, positive predictive value and negative predictive value of 86%, 75%, 97% and 37%, respectively, to differentiate between oncocytoma and renal cell carcinoma. The area under the ROC curve was 0.81. Median µOCT was significantly lower for oncocytoma vs clear cell renal cell carcinoma (3.38 vs 4.36 mm(-1), p=0.049) and for oncocytoma vs papillary renal cell carcinoma (3.38 vs 4.79 mm(-1), p=0.027). CONCLUSIONS: We demonstrated that the µOCT is significantly higher in renal cell carcinoma vs oncocytoma, with ROC analysis showing promising results for their differentiation. This demonstrates the potential of percutaneous needle based optical coherence tomography to help in the differentiation of renal masses, thus warranting ongoing research.

Focal vs extended ablation in localized prostate cancer with irreversible electroporation; a multi-center randomized controlled trial.

BACKGROUND: Current surgical and ablative treatment options for prostate cancer (PCa) may result in a high incidence of (temporary) incontinence, erectile dysfunction and/or bowel damage. These side effects are due to procedure related effects on adjacent structures including blood vessels, bowel, urethra and/or neurovascular bundle. Ablation with irreversible electroporation (IRE) has shown to be effective and safe in destroying PCa cells and also has the potential advantage of sparing surrounding tissue and vital structures, resulting in less impaired functional outcomes and maintaining men's quality of life. METHODS/DESIGN: In this randomized controlled trial (RCT) on IRE in localized PCa, 200 patients with organ-confined, unilateral (T1c-T2b) low- to intermediate-risk PCa (Gleason sum score 6 and 7) on transperineal template-mapping biopsies (TTMB) will be included. Patients will be randomized into focal or extended ablation of cancer foci with IRE. Oncological efficacy will be determined by multiparametric Magnetic Resonance Imaging, Contrast-Enhanced Ultrasound imaging if available, TTMP and Prostate Specific Antigen (PSA) follow-up. Patients will be evaluated up to 5 years on functional outcomes and quality of life with the use of standardized questionnaires. DISCUSSION: There is critical need of larger, standardized RCTs evaluating long-term oncological and functional outcomes before introducing IRE and other focal therapy modalities as an accepted and safe therapeutic option for PCa. This RCT will provide important short- and long-term data and elucidates the differences between focal or extended ablation of localized, unilateral low- to intermediate-risk PCa with IRE. TRIAL REGISTRATION: Clinicaltrials.gov database registration number NCT01835977. The Dutch Central Committee on Research Involving Human Subjects registration number NL50791.018.14.

Dynamic contrast-enhanced ultrasound parametric imaging for the detection of prostate cancer.

OBJECTIVE: To investigate the value of dynamic contrast-enhanced (DCE)-ultrasonography (US) and software-generated parametric maps in predicting biopsy outcome and their potential to reduce the amount of negative biopsy cores. MATERIALS AND METHODS: For 651 prostate biopsy locations (82 consecutive patients) we correlated the interpretation of DCE-US recordings with and without parametric maps with biopsy results. The parametric maps were generated by software which extracts perfusion parameters that differentiate benign from malignant tissue from DCE-US recordings. We performed a stringent analysis (all tumours) and a clinical analysis (clinically significant tumours). We calculated the potential reduction in biopsies (benign on imaging) and the resultant missed positive biopsies (false-negatives). Additionally, we evaluated the performance in terms of sensitivity, specificity negative predictive value (NPV) and positive predictive value (PPV) on a per-prostate level. RESULTS: Based on DCE-US, 470/651 (72.2%) of biopsy locations appeared benign, resulting in 40 false-negatives (8.5%), considering clinically significant tumours only. Including parametric maps, 411/651 (63.1%) of the biopsy locations appeared benign, resulting in 23 false-negatives (5.6%). In the per-prostate clinical analysis, DCE-US classified 38/82 prostates as benign, missing eight diagnoses. Including parametric maps, 31/82 prostates appeared benign, missing three diagnoses. Sensitivity, specificity, PPV and NPV were 73, 58, 50 and 79%, respectively, for DCE-US alone and 91, 56, 57 and 90%, respectively, with parametric maps. CONCLUSION: The interpretation of DCE-US with parametric maps allows good prediction of biopsy outcome. A two-thirds reduction in biopsy cores seems feasible with only a modest decrease in cancer diagnosis.

Thermal Energy during Irreversible Electroporation and the Influence of Different Ablation Parameters.

PURPOSE: Irreversible electroporation (IRE) uses high-voltage electric fields to achieve cell death. Although the mechanism of IRE is mainly designated as nonthermal, development of secondary Joule heating is inevitable. The study purpose was to gain understanding of temperature development and distribution during IRE. MATERIALS AND METHODS: IRE was performed in a transparent polyacrylamide gel resembling soft tissue. Mechanical effects, changes in temperature gradient, and absolute temperature changes were measured with three different optical techniques (high-speed, color Schlieren, and infrared imaging) to investigate the effect on temperature of variations in voltage, pulse length, active tip length (ATL), interelectrode distance, electrode configuration (parallel, convergent, and divergent), and sequential pulsing (pulse delivery interrupted by breaks). The total delivered energy was calculated. RESULTS: A temperature gradient, starting at the tips of both electrodes and expanding toward each other, developed immediately with pulse delivery. Temperatures increased with increasing voltage (by 2.5°C-40.4°C), pulse length (by 5.3°C-9.8°C), ATL (by 5.9°C-17.6°C), and interelectrode distance (by 7.6°C-21.5°C), in accordance with higher energy delivery. Nonparallel electrode placement resulted in heterogeneous temperature distribution with the peak temperature focused in the area with the shortest interelectrode distance. Sequential pulse delivery significantly reduced the temperature increase compared with continuous pulsing (4.3°C vs 11.7°C). CONCLUSIONS: Voltage, pulse length, interelectrode distance, ATL, and electrode configuration each have a strong effect on temperature development and distribution during IRE. Sequential pulsing reduces the extent and volume of thermal distribution and may prove beneficial with respect to procedural safety.

Chemohyperthermia in non-muscle-invasive bladder cancer: An overview of the literature and recommendations.

Non-muscle-invasive bladder cancer (NMIBC) is characterised by a high risk of recurrence for the present standard treatment of transurethral resection of the bladder (TURB) followed by intravesical instillation of Mitomycin-C (MMC) or bacillus Calmette-Guérin (BCG). To decrease this high recurrence rate, alternative treatments are studied. Intravesical MMC combined with hyperthermia could be an interesting alternative active treatment for intermediate- and high-risk NMIBC, and has been investigated in the past years. Hyperthermia, raising tumour temperatures to 40-44 °C, can be achieved with several hyperthermia systems, based on three different techniques: 1) intravesical microwave induced heating, 2) conductive heating, and 3) loco-regional, using external radiofrequency antennas. In this review an overview is given of the available hyperthermia systems and the reported outcomes. Future directions are discussed. Optimal implementation of a combined regimen of MMC and hyperthermia requires further clinical trials to identify patients who will benefit most from this treatment, to optimise treatment schedules and to compare the efficacy of different hyperthermia devices.

Prostate Cancer: Interobserver Agreement and Accuracy with the Revised Prostate Imaging Reporting and Data System at Multiparametric MR Imaging.

PURPOSE: To evaluate accuracy and interobserver variability with the use of the Prostate Imaging Reporting and Data System (PI-RADS) version 2.0 for detection of prostate cancer at multiparametric magnetic resonance (MR) imaging in a biopsy-naïve patient population. MATERIALS AND METHODS: This retrospective HIPAA-compliant study was approved by the local ethics committee, and written informed consent was obtained from all patients for use of their imaging and histopathologic data in future research studies. In 101 biopsy-naïve patients with elevated prostate-specific antigen levels who underwent multiparametric MR imaging of the prostate and subsequent transrectal ultrasonography (US)-MR imaging fusion-guided biopsy, suspicious lesions detected at multiparametric MR imaging were scored by five readers who were blinded to pathologic results by using to the newly revised PI-RADS and the scoring system developed in-house. Interobserver agreement was evaluated by using κ statistics, and the correlation of pathologic results with each of the two scoring systems was evaluated by using the Kendall τ correlation coefficient. RESULTS: Specimens of 162 lesions in 94 patients were sampled by means of transrectal US-MR imaging fusion biopsy. Results for 87 (54%) lesions were positive for prostate cancer. Kendall τ values with the PI-RADS and the in-house-developed scoring system, respectively, at T2-weighted MR imaging in the peripheral zone were 0.51 and 0.17 and in the transitional zone, 0.45 and -0.11; at diffusion-weighted MR imaging, 0.42 and 0.28; at dynamic contrast material-enhanced MR imaging, 0.23 and 0.24, and overall suspicion scores were 0.42 and 0.49. Median κ scores among all possible pairs of readers for PI-RADS and the in-house-developed scoring system, respectively, for T2-weighted MR images in the peripheral zone were 0.47 and 0.15; transitional zone, 0.37 and 0.07; diffusion-weighted MR imaging, 0.41 and 0.57; dynamic contrast-enhanced MR imaging, 0.48 and 0.41; and overall suspicion scores, 0.46 and 0.55. CONCLUSION: Use of the revised PI-RADS provides moderately reproducible MR imaging scores for detection of clinically relevant disease.

Combining Mitomycin C and Regional 70 MHz Hyperthermia in Patients with Nonmuscle Invasive Bladder Cancer: A Pilot Study.

PURPOSE: Despite intravesical therapy with immunotherapy or chemotherapy intermediate and high risk nonmuscle invasive bladder cancer is associated with a high risk of recurrence and progression to muscle invasive bladder carcinoma. While intravesical hyperthermia combined with mitomycin C has proved effective to treat nonmuscle invasive bladder cancer, there is less experience with invasive regional 70 MHz hyperthermia and mitomycin C. Therefore, we examined the safety and feasibility of this treatment combination for intermediate and high risk nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Between 2009 and 2011, 20 patients with intermediate and high risk nonmuscle invasive bladder cancer were treated with intravesical mitomycin C (40 mg) combined with regional hyperthermia. Treatment consisted of 6 weekly sessions followed by a maintenance period of 1 year with 1 hyperthermia-mitomycin C session every 3 months. Regional hyperthermia was administered using a 70 MHz phased array system with 4 antennas. Toxicity was scored using CTC (Common Toxicity Criteria) 3.0. RESULTS: The records of 18 of 20 patients could be analyzed. Median followup was 46 months. Of the 18 patients 15 (83%) completed the induction period of 6 treatments. Four patients (22%) discontinued treatment because of physical complaints without exceeding grade 2 toxicity. Toxicity scored according to CTC 3.0 was limited to grade 1 in 43% of cases and grade 2 in 14%. Mean T90 and T50 bladder temperatures were 40.6C and 41.6C, respectively. The 24-month recurrence-free survival rate was 78%. CONCLUSIONS: Treatment with regional hyperthermia combined with mitomycin C in patients with intermediate and high risk nonmuscle invasive bladder cancer is feasible with low toxicity and excellent bladder temperatures.