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BACKGROUND Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. METHODS In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. RESULTS A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [Cl], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was non inferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% Cl, -19 to -7; PcO.OOl). CONCLUSIONS The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION CIinicalTrials.gov number, NCT02380027.) [ABSTRACT FROM AUTHOR]

Background and Objective: Magnetic resonance imaging (MRI) can detect recurrences after focal therapy for prostate cancer but there is no robust guidance regarding its use. Our objective was to produce consensus recommendations on MRI acquisition, interpretation, and reporting after focal therapy., Methods: A systematic review was performed in July 2022 to develop consensus statements. A two-round consensus exercise was then performed, with a consensus meeting in January 2023, during which 329 statements were scored by 23 panellists from Europe and North America spanning urology, radiology, and pathology with experience across eight focal therapy modalities. Using RAND Corporation/University of California-Los Angeles methodology, the Transatlantic Recommendations for Prostate Gland Evaluation with MRI after Focal Therapy (TARGET) were based on consensus for statements scored with agreement or disagreement., Key Findings and Limitations: In total, 73 studies were included in the review. All 20 studies (100%) reporting suspicious imaging features cited focal contrast enhancement as suspicious for cancer recurrence. Of 31 studies reporting MRI assessment criteria, the Prostate Imaging-Reporting and Data System (PI-RADS) score was the scheme used most often (20 studies; 65%), followed by a 5-point Likert score (six studies; 19%). For the consensus exercise, consensus for statements scored with agreement or disagreement increased from 227 of 295 statements (76.9%) in round one to 270 of 329 statements (82.1%) in round two. Key recommendations include performing routine MRI at 12 mo using a multiparametric protocol compliant with PI-RADS version 2.1 standards. PI-RADS category scores for assessing recurrence within the ablation zone should be avoided. An alternative 5-point scoring system is presented that includes a major dynamic contrast enhancement (DCE) sequence and joint minor diffusion-weighted imaging and T2-weighted sequences. For the DCE sequence, focal nodular strong early enhancement was the most suspicious imaging finding. A structured minimum reporting data set and minimum reporting standards for studies detailing MRI data after focal therapy are presented., Conclusions and Clinical Implications: The TARGET consensus recommendations may improve MRI acquisition, interpretation, and reporting after focal therapy for prostate cancer and provide minimum standards for study reporting., Patient Summary: Magnetic resonance imaging (MRI) scans can detect recurrent of prostate cancer after focal treatments, but there is a lack of guidance on MRI use for this purpose. We report new expert recommendations that may improve practice., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Prior history of transurethral resection of the prostate (TURP) can complicate Robot-assisted radical prostatectomy (RARP). Very few studies analyse the outcomes of RARP in men with a prior history of TURP. We analysed the oncological and functional outcomes of RARP in post-TURP men from our prospectively maintained database. We included the RARP data from January 2016 to January 2022. Thirty men who had RARP with a prior history of TURP were identified (Group 2). They were matched using R software and propensity score matching to 90 men with no previous TURP (Group-1). The groups were matched for age, body mass index (BMI), Gleason score, stage, PSA and D'Amico risk category in a 1:3 ratio. The two-year oncological and functional outcomes were compared. Overall, the study found no significant difference between the groups in the preoperative parameters, such as BMI, age, Gleason grade, clinical stage, PSA, prostate volume, and D'amico risk grouping. There was no difference in the estimated blood loss. The TURP group had a lower chance of having a nerve spare (p = 0.03). The median console time was longer in the TURP group (140 min (120,180) versus 168 (129,190) p = 0.058). The postoperative complications (Clavien-Dindo 3a 2% versus 6.7%) and hospital stay (median of 2 days), positive surgical margins, continence, and biochemical recurrence rates at 3, 12, and 24 months were not statistically different between the groups. In high-volume centres, the oncological and continence outcomes of RARP post-TURP are not inferior to that of men without prior TURP., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Benign prostatic hyperplasia (BPH) is a common condition amongst older men and is associated with lower urinary tract symptoms and erectile dysfunction; these symptoms can be burdensome and negatively affect quality of life. Various surgical and pharmaceutical treatment options exist but there is a paucity of qualitative research exploring men's decision-making when seeking BPH treatment. This study qualitatively explored men's experience of living with BPH and seeking treatment for BPH. Twenty men (aged 52-75) were recruited from outpatient urology clinics at a hospital trust in Southern England. Data were collected using semi-structured interviews (via video or telephone call) and were audio-recorded; transcripts were analysed using thematic analysis. Four themes were generated: 'Impacts are about more than just physical symptoms', 'The path towards treatment', 'The process of information gathering' and 'Navigating hopes, fears and uncertainty'. Results indicate most men appear to seek treatment for BPH following a gradual, and sometimes lengthy, period of deterioration in symptoms; for some men, however, treatment seeking follows an acute episode of sudden or severe symptoms. The decision to proceed with surgical or minimally invasive treatment options appears to be dependent on men reaching a tipping point; they no longer perceive their symptoms as tolerable and feel their ability to cope with symptoms is reduced. Men each bring their own set of concerns and preferences about side effects and risk-benefit profiles of different treatments. Clinicians need to be sensitive to these individual differences and incorporate them into shared decision-making for choosing between treatment options for BPH.

Background: Rezūm water vapour ablation is an effective minimally invasive surgical therapy for the treatment of bladder outflow obstruction., Objective: To present early outcomes and reoperation rates after Rezūm, including an analysis of retreatment rates to gain an insight into optimal patient selection and the durability of the procedure., Design Setting and Participants: Data were prospectively collected for consecutive patients undergoing Rezūm for symptomatic benign prostatic hyperplasia between March 2017 and January 2020 at two hospital sites., Intervention: Rezūm treatment of the prostate., Outcome Measurements and Statistical Analysis: Patients were reviewed at 6 wk and 3, 6, and 12 mo after their Rezūm procedure. We evaluated changes in urinary symptoms and the retreatment rate., Results and Limitations: A total of 461 patients undergoing Rezūm were analysed. The mean (±standard deviation) follow-up duration was 16.7 ± 10.4 mo. The mean patient age was 67.5 ± 7.8 yr and the mean prostate volume was 56.5 ± 24.0 ml. There was a significant improvement in mean maximum flow rate and postvoid residual volume and in International Prostate Symptom Score and quality-of-life scores ( p  < 0.0001). During the follow-up period, 21 patients (4.6%) required retreatment, of which 11 cases (2.4%) were within the first year. The retreatments included eight bladder neck incisions or resections, six transurethral resections of the prostate, four Greenlight laser photoselective vaporisations of the prostate, and three Rezūm procedures. The median length of time to a further operation was 11.5 mo (range 3-34). The most common findings at reoperation were an inadequately treated median lobe, an obstructing bladder neck, and in some cases asymmetry of the prostate cavity or recesses within the prostate gland., Conclusions: This study demonstrates that the beneficial effects of Rezūm observed in the pivotal phase 2 randomised study are transferable to a real-world population with a comparable early retreatment rate. A range of procedures were used for retreatment. The factors dictating which option to select were based on patient concerns regarding side effects, gland volume, symptom profile, and cystoscopy findings., Patient Summary: We investigated outcomes for patients undergoing Rezūm, a water vapour treatment to reduce the size of the prostate in men with obstruction of the bladder outlet because of benign prostate enlargement. This technique yields significant improvements in symptoms and preserves sexual function. The proportion of men needing retreatment was 2.4% in the first year after their Rezūm procedure., (© 2022 The Authors.)

Purpose of Review: This review aims to give a brief description of the latest minimally invasive surgical techniques (MISTs) for the treatment of benign prostatic obstruction (BPO)., Recent Findings: In recent years technological advances have made the implementation of MISTs in the armamentarium of BPO surgery possible and in many cases could replace standard procedures.These techniques offer many advantages -short recovery time, rapid symptomatic relief, few adverse effects, lower risk of sexual/ejaculatory dysfunction, acceptable durability and most can be performed as an outpatient procedure.Many of the newer MISTs can be performed outside the operating room under local anesthesia, hence the term office-based MIST., Summary: A tailored BPO surgical treatment should not only take into account the prostate volume, but also many other factors including possible adverse events and the patient's expectations.Further studies and long-term data are necessary to standardize methods for evaluating the outcomes of these new procedures and to see which will pass the test of time and end-up replacing the gold standard procedures., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Focal therapy (FT) ablates areas of prostate cancer rather than treating the whole gland. We compared oncological outcomes of FT to radical prostatectomy (RP)., Methods: Using prospective multicentre databases of 761 FT and 572 RP cases (November/2005-September/2018), patients with PSA < 20 ng/ml, Gleason 

Gleason score 7 prostate cancer with a higher proportion of pattern 4 (G4) has been linked to genomic heterogeneity and poorer patient outcome. The current assessment of G4 proportion uses estimation by a pathologist, with a higher proportion of G4 more likely to trigger additional imaging and treatment over active surveillance. This estimation method has been shown to have inter-observer variability. Fifteen patients with Prostate Grade Group (GG) 2 (Gleason 3 + 4) and fifteen patients with GG3 (Gleason 4 + 3) disease were selected from the PROMIS study with 192 haematoxylin and eosin-stained slides scanned. Two experienced uropathologists assessed the maximum cancer core length (MCCL) and G4 proportion using the current standard method (visual estimation) followed by detailed digital manual annotation of each G4 area and measurement of MCCL (planimetric estimation) using freely available software by the same two experts. We aimed to compare visual estimation of G4 and MCCL to a pathologist-driven digital measurement. We show that the visual and digital MCCL measurement differs up to 2 mm in 76.6% (23/30) with a high degree of agreement between the two measurements; Visual gave a median MCCL of 10 ± 2.70 mm (IQR 4, range 5-15 mm) compared to digital of 9.88 ± 3.09 mm (IQR 3.82, range 5.01-15.7 mm) (p = 0.64) The visual method for assessing G4 proportion over-estimates in all patients, compared to digital measurements [median 11.2% (IQR 38.75, range 4.7-17.9%) vs 30.4% (IQR 18.37, range 12.9-50.76%)]. The discordance was higher as the amount of G4 increased (Bias 18.71, CI 33.87-48.75, r 0.7, p < 0.0001). Further work on assessing actual G4 burden calibrated to clinical outcomes might lead to the use of differing G4 thresholds of significance if the visual estimation is used or by incorporating semi-automated methods for G4 burden measurement.

Background: Multiparametric magnetic resonance imaging (MP-MRI) is established in the diagnosis of prostate cancer, but the need for enhanced sequences has recently been questioned., Objective: To assess whether dynamic contrast-enhanced imaging (DCE) improves accuracy over T2 and diffusion sequences., Design, Setting, and Participants: PROMIS was a multicentre, multireader trial, with, in this part, 497 biopsy-naïve men undergoing standardised 1.5T MP-MRI using T2, diffusion, and DCE, followed by a detailed transperineal prostate mapping (TPM) biopsy at 5 mm intervals. Likert scores of 1-5 for the presence of a significant tumour were assigned in strict sequence, for (1) T2 + diffusion and then (2) T2 + diffusion + dynamic contrast-enhanced images., Outcome Measurements and Statistical Analysis: For the primary analysis, the primary PROMIS outcome measure (Gleason score ≥4 + 3 or ≥6 mm maximum cancer length) on TPM was used, and an MRI score of ≥3 was considered positive., Results and Limitations: Sensitivity without and with DCE was 94% and 95%, specificity 37% and 38%, positive predictive value 51% and 51%, and negative predictive value 90% and 91%, respectively (p >  0.05 in each case). The number of patients avoiding biopsy (scoring 1-2) was similar (123/497 vs 121/497, p =  0.8). The number of equivocal scores (3/5) was slightly higher without DCE (32% vs 28% p =  0.031). The proportion of MRI equivocal (3/5) and positive (4-5) cases showing significant tumours were similar (23% and 71% vs 20% and 69%). No cases of dominant Gleason 4 or higher were missed with DCE, compared with a single case with T2 + diffusion-weighted imaging. No attempt was made to correlate lesion location on MRI and histology, which may be considered a limitation. Radiologists were aware of the patient's prostate-specific antigen., Conclusions: Contrast adds little when MP-MRI is used to exclude significant prostate cancer., Patient Summary: An intravenous injection of contrast may not be necessary when magnetic resonance imaging is used as a test to rule out significant tumours in the prostate., (Copyright © 2020. Published by Elsevier B.V.)

Background: Prostate biopsy guided by magnetic resonance imaging (MRI) is increasingly used to obtain tissue from men with suspected prostate cancer (PC)., Objective: To report a multicentre series of image-fusion transperineal prostate biopsies and compare the diagnostic yield of clinically significant PC (csPC) between targeted and nontargeted biopsies., Design, Setting, and Participants: The study included 640 consecutive patients with elevated prostate specific antigen (PSA) presenting for first biopsy or following a previous negative transrectal biopsy under the care of 13 urologists in 11 centres in the UK (April 2014-June 2017)., Intervention: Multiparametric MRI was carried out in 61 approved prostate MRI centres with transperineal targeted alone (n=283) or targeted plus nontargeted (n=357) transperineal rigid image-fusion targeted biopsy (MIM-Symphony-DX)., Outcome Measurements and Statistical Analysis: Rates of csPC and insignificant cancer detection in targeted and nontargeted biopsies were measured using a number of thresholds to define clinical significance. The primary definition was Gleason≥4+3 or any grade ≥6mm., Results and Limitations: The mean age, median PSA, and median prostate volume for the cohort were 63.8yr (standard deviation [SD] 8.4), 6.3 ng/ml (SD 5.8), and 42.0cm 3 (SD 24.7), respectively. Overall, 276/640 men (43.1%) were diagnosed with csPC. csPC was detected from targeted biopsies alone in 263/640 cases (41.1%). Of the 357 men who underwent nontargeted biopsies, three (0.8%) had csPC exclusively in nontargeted cores, with no evidence of cancer in targeted cores. Overall, 32/357 (9.0%) had csPC in nontargeted biopsies regardless of the targeted biopsy findings. Clinically insignificant disease in nontargeted biopsies was detected in 93/357 men (26.1%). Our findings were consistent across all other thresholds of clinical significance. Limitations include the lack of nontargeted biopsies in all men., Conclusions: In this large multicentre series, nontargeted prostate biopsy cores had a low yield of csPC and a high yield of clinically insignificant PC. An image-fusion targeted-biopsy-only approach maintains high detection for csPC and low detection of clinically insignificant cancers., Patient Summary: In this report, we found that following prostate multiparametric magnetic resonance imaging and targeted transperineal biopsies of suspicious areas, the clinical value of performing additional extensive unguided biopsies of nonsuspicious areas is limited and can often find insignificant cancers that do not need treatment., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: We evaluated the performance of transrectal ultrasound guided systematic and transperineal template mapping biopsies with a 5 mm sampling frame stratified by the multiparametric magnetic resonance imaging Likert score in the PROMIS (Prostate MR Imaging Study)., Materials and Methods: Biopsy naïve men due to undergo prostate biopsy for elevated prostate specific antigen and/or abnormal digital rectal examination underwent multiparametric magnetic resonance imaging, and transperineal template mapping and transrectal ultrasound guided systematic biopsies, which were performed and reported while blinded to other test results. Clinically significant prostate cancer was primarily defined as Gleason 4 + 3 or greater, or a maximum cancer core length of 6 mm or more of any grade. It was secondarily defined as Gleason 3 + 4 or greater, or a maximum cancer core length of 4 mm or more of any grade., Results: In 41 months 740 men were recruited at a total of 11 centers, of whom 576 underwent all 3 tests. Eight of the 150 men (5.1%) with a multiparametric magnetic resonance imaging score of 1-2 had any Gleason 3 + 4 or greater disease on transrectal ultrasound guided systematic biopsy. Of the 75 men in whom transrectal ultrasound guided systematic biopsy showed Gleason 3 + 3 of any maximum cancer core length 61 (81%) had Gleason 3 + 4, 8 (11%) had Gleason 4 + 3 and 0 (0%) had Gleason 4 + 5 or greater disease. For definition 1 (clinically significant prostate cancer) transrectal ultrasound guided systematic biopsy sensitivity remained stable and low across multiparametric magnetic resonance imaging Likert scores of 35% to 52%. For definition 2 (clinically significant prostate cancer and any cancer) sensitivity increased with higher multiparametric magnetic resonance imaging scores. The negative predictive value varied due to varying disease prevalence but for all cancer thresholds it declined with increasing multiparametric magnetic resonance imaging scores., Conclusions: In the setting of multiparametric magnetic resonance imaging Likert scores 1-2 transrectal ultrasound guided systematic biopsy revealed Gleason 3 + 4 disease in only 1 of 20 men. Further, for any clinically significant prostate cancer definition transrectal ultrasound guided systematic biopsy had poor sensitivity and variable but a low negative predictive value across multiparametric magnetic resonance imaging scores. Men who undergo transrectal ultrasound guided systematic biopsy without targeting in the setting of a multiparametric magnetic resonance imaging score of 3 to 5 should be advised to undergo repeat (targeted) biopsy.

Objective: To describe how clinicians conceptualised equipoise in the PART (Partial prostate Ablation vs Radical prosTatectomy in intermediate-risk unilateral clinically localised prostate cancer) feasibility study and how this affected recruitment., Subjects and Methods: PART included a QuinteT Recruitment Intervention (QRI) to optimise recruitment. Phase I aimed to understand recruitment, and included: scrutinising recruitment data, interviewing the trial management group and recruiters (n = 13), and audio-recording recruitment consultations (n = 64). Data were analysed using qualitative content and thematic analysis methods. In Phase II, strategies to improve recruitment were developed and delivered., Results: Initially many recruiters found it difficult to maintain a position of equipoise and held preconceptions about which treatment was best for particular patients. They did not feel comfortable about approaching all eligible patients, and when the study was discussed, biases were conveyed through the use of terminology, poorly balanced information, and direct treatment recommendations. Individual and group feedback led to presentations to patients becoming clearer and enabled recruiters to reconsider their sense of equipoise. Although the precise impact of the QRI alone cannot be determined, recruitment increased (from a mean [range] of 1.4 [0-4] to 4.5 [0-12] patients/month) and the feasibility study reached its recruitment target., Conclusion: Although clinicians find it challenging to recruit patients to a trial comparing different contemporary treatments for prostate cancer, training and support can enable recruiters to become more comfortable with conveying equipoise and providing clearer information to patients., (© 2018 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Prostate cancer (PCa) is the most common cancer in men in the UK. Patients with intermediate-risk, clinically localised disease are offered radical treatments such as surgery or radiotherapy, which can result in severe side effects. A number of alternative partial ablation (PA) technologies that may reduce treatment burden are available; however the comparative effectiveness of these techniques has never been evaluated in a randomised controlled trial (RCT)., Objectives: To assess the feasibility of a RCT of PA using high-intensity focused ultrasound (HIFU) versus radical prostatectomy (RP) for intermediate-risk PCa and to test and optimise methods of data capture., Design: We carried out a prospective, multicentre, open-label feasibility study to inform the design and conduct of a future RCT, involving a QuinteT Recruitment Intervention (QRI) to understand barriers to participation., Setting: Five NHS hospitals in England., Participants: Men with unilateral, intermediate-risk, clinically localised PCa., Interventions: Radical prostatectomy compared with HIFU., Primary Outcome Measure: The randomisation of 80 men., Secondary Outcome Measures: Findings of the QRI and assessment of data capture methods., Results: Eighty-seven patients consented to participate by 31 March 2017 and 82 men were randomised by 4 May 2017 (41 men to the RP arm and 41 to the HIFU arm). The QRI was conducted in two iterative phases: phase I identified a number of barriers to recruitment, including organisational challenges, lack of recruiter equipoise and difficulties communicating with patients about the study, and phase II comprised the development and delivery of tailored strategies to optimise recruitment, including group training, individual feedback and 'tips' documents. At the time of data extraction, on 10 October 2017, treatment data were available for 71 patients. Patient characteristics were similar at baseline and the rate of return of all clinical case report forms (CRFs) was 95%; the return rate of the patient-reported outcome measures (PROMs) questionnaire pack was 90.5%. Centres with specific long-standing expertise in offering HIFU as a routine NHS treatment option had lower recruitment rates (Basingstoke and Southampton) - with University College Hospital failing to enrol any participants - than centres offering HIFU in the trial context only., Conclusions: Randomisation of men to a RCT comparing PA with radical treatments of the prostate is feasible. The QRI provided insights into the complexities of recruiting to this surgical trial and has highlighted a number of key lessons that are likely to be important if the study progresses to a main trial. A full RCT comparing clinical effectiveness, cost-effectiveness and quality-of-life outcomes between radical treatments and PA is now warranted., Future Work: Men recruited to the feasibility study will be followed up for 36 months in accordance with the protocol. We will design a full RCT, taking into account the lessons learnt from this study. CRFs will be streamlined, and the length and frequency of PROMs and resource use diaries will be reviewed to reduce the burden on patients and research nurses and to optimise data completeness., Trial Registration: Current Controlled Trials ISRCTN99760303., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 22, No. 52. See the NIHR Journals Library website for further project information., Competing Interests: Ray Fitzpatrick is a member of the Health Technology Assessment Priority Research Advisory Methods Group. Richard Hindley has received payments for lecturing and proctoring for SonaCare Medical (Charlotte, NC, USA; high-intensity focused ultrasound treatment). Hashim U Ahmed reports grants and personal fees from SonaCare Medical and grants from Trod Medical (Heverlee, Belgium) and Sophiris Bio Inc. (La Jolla, CA, USA) outside the submitted work.

Introduction: When performing open or laparoscopic nephroureterectomy (LNU), the optimal way to excise the distal ureter remains controversial. There are concerns that primary endoscopic detachment of the intramural ureter is associated with adverse outcomes. Existing studies have limited number of patients and inadequate oncologic follow-up. We provide our institutions experience of this technique., Materials and Methods: Data were collected prospectively on 59 patients (37 men) who underwent LNU for a 10-year period at a single center using a standardized technique: initial endoscopic circumferential release of the distal ureter and bladder cuff followed by retroperitoneal en bloc LNU., Results: Patients had a mean age of 67 years and Charlson score of 2. One case was converted to open surgery. Mean operative time was 194 minutes with estimated blood loss of 125 mL. Three patients (5%) required a blood transfusion. Mean in-patient stay was 3 days. Forty-six patients had urothelial carcinoma. Seventy-one percent of patients had high-grade disease (n = 33) and 21% had distal ureteral disease (n = 10). One patient required open excision of recurrence at the site of the excised ureteral orifice and remains disease free 5 years later. Five-year cancer-specific survival was 100% for patients with stages pTa (n = 7) and pT1 (n = 14), 93% for stage pT2 (n = 7) disease, and 49% for patients with stage pT3 (n = 18) disease., Conclusions: Transurethral resection of the ureteral orifice during LNU achieves acceptable long-term oncologic outcomes while minimizing perioperative morbidity and in-patient stay. This represents the largest single-center study of this technique to date.

Background: The GOLIATH study is a 2-yr trial comparing transurethral resection of prostate (TURP) to photoselective vaporization with the GreenLight XPS Laser System (GL-XPS) for the treatment of benign prostatic obstruction (BPO). Noninferiority of GL-XPS to TURP was demonstrated based on a 6-mo follow-up from the study., Objective: To determine whether treatment effects observed at 6 mo between GL-XPS and TURP was maintained at the 2-yr follow-up., Design, Setting, and Participants: Prospective randomized controlled trial at 29 centers in nine European countries involving 281 patients with BPO., Intervention: Photoselective vaporization using the 180-W GreenLight GL-XPS or conventional (monopolar or bipolar) TURP., Outcome Measurements and Statistical Analysis: The primary outcome was the International Prostate Symptom Score for which a margin of three was used to evaluate the noninferiority of GL-XPS. Secondary outcomes included Qmax, prostate volume, prostate specific antigen, Overactive Bladder Questionnaire Short Form, International Consultation on Incontinence Questionnaire Short Form, occurrence of surgical retreatment, and freedom from complications., Results and Limitations: One hundred and thirty-six patients were treated using GL-XPS and 133 using TURP. Noninferiority of GL-XPS on International Prostate Symptom Score, Qmax, and freedom from complications was demonstrated at 6-mo and was sustained at 2-yr. The proportion of patients complication-free through 24-mo was 83.6% GL-XPS versus 78.9% TURP. Reductions in prostate volume and prostate specific antigen were similar in both arms and sustained over the course of the trial. Compared with the 1(st) yr of the study, very few adverse events or retreatments were reported in either arm. Treatment differences in the Overactive Bladder Questionnaire Short Form observed at 12-mo were not statistically significant at 24-mo. A limitation was that patients and treating physicians were not blinded to the therapy., Conclusions: Twenty-four-mo follow-up data demonstrated that GL-XPS provides a durable surgical option for the treatment of BPO that exhibits efficacy and safety outcomes similar to TURP., Patient Summary: The long-term effectiveness and safety of GLP-XLS was similar to conventional TURP for the treatment of prostate enlargement., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Transrectal ultrasound-guided prostate biopsies are prone to detection errors. Multi-parametric MRI (MP-MRI) may improve the diagnostic pathway., Methods: PROMIS is a prospective validating paired-cohort study that meets criteria for level 1 evidence in diagnostic test evaluation. PROMIS will investigate whether multi-parametric (MP)-MRI can discriminate between men with and without clinically-significant prostate cancer who are at risk prior to first biopsy. Up to 714 men will have MP-MRI (index), 10-12 core TRUS-biopsy (standard) and 5mm transperineal template mapping (TPM) biopsies (reference). The conduct and reporting of each test will be blinded to the others., Results: PROMIS will measure and compare sensitivity, specificity, and positive and negative predictive values of both MP-MRI and TRUS-biopsy against TPM biopsies. The MP-MRI results will be used to determine the proportion of men who could safely avoid biopsy without compromising detection of clinically-significant cancers. For the primary outcome, significant cancer on TPM is defined as Gleason grade >/= 4+3 and/or maximum cancer core length of ≥ 6 mm. PROMIS will also assess inter-observer variability among radiologists among other secondary outcomes. Cost-effectiveness of MP-MRI prior to biopsy will also be evaluated., Conclusions: PROMIS will determine whether MP-MRI of the prostate prior to first biopsy improves the detection accuracy of clinically-significant cancer., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Focal therapy as a treatment option for localized prostate cancer (PCa) is an increasingly popular and rapidly evolving field., Objective: To gather expert opinion on patient selection, interventions, and meaningful outcome measures for focal therapy in clinical practice and trial design., Design, Setting, and Participants: Fifteen experts in focal therapy followed a modified two-stage RAND/University of California, Los Angeles (UCLA) Appropriateness Methodology process. All participants independently scored 246 statements prior to rescoring at a face-to-face meeting. The meeting occurred in June 2013 at the Royal Society of Medicine, London, supported by the Wellcome Trust and the UK Department of Health., Outcome Measurements and Statistical Analysis: Agreement, disagreement, or uncertainty were calculated as the median panel score. Consensus was derived from the interpercentile range adjusted for symmetry level., Results and Limitations: Of 246 statements, 154 (63%) reached consensus. Items of agreement included the following: patients with intermediate risk and patients with unifocal and multifocal PCa are eligible for focal treatment; magnetic resonance imaging-targeted or template-mapping biopsy should be used to plan treatment; planned treatment margins should be 5mm from the known tumor; prostate volume or age should not be a primary determinant of eligibility; foci of indolent cancer can be left untreated when treating the dominant index lesion; histologic outcomes should be defined by targeted biopsy at 1 yr; residual disease in the treated area of ≤3 mm of Gleason 3+3 did not need further treatment; and focal retreatment rates of ≤20% should be considered clinically acceptable but subsequent whole-gland therapy deemed a failure of focal therapy. All statements are expert opinion and therefore constitute level 5 evidence and may not reflect wider clinical consensus., Conclusions: The landscape of PCa treatment is rapidly evolving with new treatment technologies. This consensus meeting provides guidance to clinicians on current expert thinking in the field of focal therapy., Patient Summary: In this report we present expert opinion on patient selection, interventions, and meaningful outcomes for clinicians working in focal therapy for prostate cancer., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: We present the 1-year results of the GOLIATH prospective randomized controlled trial comparing transurethral resection of the prostate to GreenLight XPS for the treatment of men with nonneurogenic lower urinary tract symptoms due to prostate enlargement. The updated results at 1 year show that transurethral resection of the prostate and GreenLight XPS remain equivalent, and confirm the therapeutic durability of both procedures. We also report 1-year followup data from several functional questionnaires (OABq-SF, ICIQ-SF and IIEF-5) and objective assessments., Materials and Methods: A total of 291 patients were enrolled at 29 sites in 9 European countries. Patients were randomized 1:1 to undergo GreenLight XPS or transurethral resection of the prostate. The trial was designed to evaluate the hypothesis that GreenLight XPS is noninferior to transurethral resection of the prostate on the International Prostate Symptom Score at 6 months. Several objective parameters were assessed, including maximum urinary flow rate, post-void residual urine volume, prostate volume and prostate specific antigen, in addition to functional questionnaires and adverse events at each followup., Results: Of the 291 enrolled patients 281 were randomized and 269 received treatment. Noninferiority of GreenLight XPS was maintained at 12 months. Maximum urinary flow rate, post-void residual urine volume, prostate volume and prostate specific antigen were not statistically different between the treatment arms at 12 months. The complication-free rate at 1 year was 84.6% after GreenLight XPS vs 80.5% after transurethral resection of the prostate. At 12 months 4 patients treated with GreenLight XPS and 4 who underwent transurethral resection of the prostate had unresolved urinary incontinence., Conclusions: Followup at 1 year demonstrated that photoselective vaporization of the prostate produced efficacy outcomes similar to those of transurethral resection of the prostate. The complication-free rates and overall reintervention rates were comparable between the treatment groups., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The comparative outcome with GreenLight (GL) photoselective vaporisation of the prostate and transurethral resection of the prostate (TURP) in men with lower urinary tract symptoms due to benign prostatic obstruction (BPO) has been questioned., Objective: The primary objective of the GOLIATH study was to evaluate the noninferiority of 180-W GL XPS (XPS) to TURP for International Prostate Symptom Score (IPSS) and maximum flow rate (Qmax) at 6 mo and the proportion of patients who were complication free., Design, Setting, and Participants: Prospective randomised controlled trial at 29 centres in 9 European countries involving 281 patients with BPO., Intervention: 180-W GL XPS system or TURP., Outcome Measurements and Statistical Analysis: Measurements used were IPSS, Qmax, prostate volume (PV), postvoid residual (PVR) and complications, perioperative parameters, and reintervention rates. Noninferiority was evaluated using one-sided tests at the 2.5% level of significance. The statistical significance of other comparisons was assessed at the (two-sided) 5% level., Results and Limitations: The study demonstrated the noninferiority of XPS to TURP for IPSS, Qmax, and complication-free proportion. PV and PVR were comparable between groups. Time until stable health status, length of catheterisation, and length of hospital stay were superior with XPS (p<0.001). Early reintervention rate within 30 d was three times higher after TURP (p=0.025); however, the overall postoperative reintervention rates were not significantly different between treatment arms. A limitation was the short follow-up., Conclusions: XPS was shown to be noninferior (comparable) to TURP in terms of IPSS, Qmax, and proportion of patients free of complications. XPS results in a lower rate of early reinterventions but has a similar rate after 6 mo., Trial Registration: ClinicalTrials.gov, identifier NCT01218672., (Copyright © 2013. Published by Elsevier B.V.)

Introduction: Focal therapy offers the possibility of cancer control, without the side effect profile of radical therapies. Early single centre prospective development studies using high intensity focused ultrasound (HIFU) have demonstrated encouraging genitourinary functional preservation and short-term cancer control. Large multi-centre trials are required to evaluate medium-term cancer control and reproduce functional recovery. We describe the study design of an investigator-led UK multi-centre, single arm trial using HIFU to deliver focal therapy for men with localised prostate cancer., Methods: One-hundred and forty men with histologically proven localised low or intermediate risk prostate cancer (PSA < 15, Gleason ≤ 7, ≤ T2cN0M0) will undergo precise characterisation of the prostate using a combination of multi-parametric (mp)MRI and transperineal template prostate mapping (TPM) biopsies. Unilateral dominant tumours, the so-called index lesion, will be eligible for treatment provided the contra-lateral side is free of 'clinically significant' disease (as defined by Gleason ≥ 7 or maximum cancer core length ≥4 mm). Patients will receive focal therapy using HIFU (Sonablate 500®). Treatment effect will be assessed by targeted biopsies of the treated area and TPM biopsies at 36-months., Results: Primary outcome is the absence of clinically significant disease based on 36-month post-treatment TPM biopsies. Secondary outcomes address a) genitourinary function using validated patient questionnaires (IPSS, IPSS-QoL, IIEF-15, EPIC-Urinary, EPIC-Bowel, FACT-P, EQ-5D), b) the predictive validity of imaging, and c) risk factors for treatment failure., Conclusions: INDEX will be the first multi-centre, medium term follow-up trial to evaluate the outcomes of a tissue preserving strategy for men with localised prostate cancer using the TPM-ablate-TPM strategy., (Copyright © 2013. Published by Elsevier Inc.)

Purpose: Prostate cancer (PC) is the second most common cause of cancer related death in men. A number of key limitations with prostate specific antigen (PSA), currently the standard detection test, has justified evaluation of new biomarkers. We have assessed the diagnostic potential of Engrailed-2 (EN2) protein, a homeodomain-containing transcription factor expressed in PC cell lines and secreted into the urine by PC in men., Experimental Design: EN2 expression in PC cell lines and prostate cancer tissue was determined by semi-quantative RT-PCR and immunohistochemistry. First pass urine [without prior digital rectal examination (DRE)] was collected from men presenting with urinary symptoms (referred to exclude/confirm the presence of prostate cancer) and from controls. EN2 protein was measured by ELISA in urine from men with PC (n = 82) and controls (n = 102)., Results: EN2 was expressed and secreted by PC cell lines and PC tissue but not by normal prostate tissue or stroma. The presence of EN2 in urine was highly predictive of PC, with a sensitivity of 66% and a specificity of 88.2%, without requirement for DRE. There was no correlation with PSA levels. These results were confirmed independently by a second academic center., Conclusions: Urinary EN2 is a highly specific and sensitive candidate biomarker of prostate cancer. A larger multicenter study to further evaluate the diagnostic potential of EN2 is justified., (©2011 AACR.)

We report for the first time evidence of flow-induced polymer degradation during inkjet printing for both poly(methyl methacrylate) (PMMA) and polystyrene (PS) in good solvent. This has significance for the deposition of functional and biological materials. Polymers having Mw either less than 100 kDa or greater than approximately 1,000 kDa show no evidence of molecular weight degradation. The lower boundary condition is a consequence of low Deborah Number De imposed by the printhead geometry and the upper boundary condition due to visco-elastic damping. For intermediate molecular weights the effect is greatest at high elongational strain rate and low solution concentration with higher polydispersity polymers being most sensitive to molecular weight degradation. For low polydispersity samples, PDi ≤ 1.3, chain breakage is essentially centro-symmetric induced either by turbulance or overstretching when the strain rate increases well beyond a critical value, that is the stretching rate is high enough to exceed the rate of relaxation. For higher polydispersity samples chain breakage is consistent with almost random scission along the chain, inferring that the forces required to break the chain are additionally transmitted either by valence bonds, i.e. network chains and junctions or discrete entanglements rather than solely by hydrodynamic interaction., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Metastatic renal cell carcinoma is associated with a poor prognosis. Given the current lack of effective systemic therapies and data suggesting a survival benefit from cytoreductive nephrectomy (CRN) before systemic therapy, we have retrospectively analyzed the experience of laparoscopic cytoreductive nephrectomy (LCRN) in three U.K. centers. The focus of this study was to assess the peri- and postoperative safety and hence feasibility of LCRN in the United Kingdom., Patients and Methods: Twenty-five patients with metastatic renal cell carcinoma deemed suitable for systemic therapy underwent LCRN in three U.K. centers over a 4-year period., Results: The tumors ranged from 3.4 cm in diameter to 12 cm. Operating times ranged from 89 (minimum) to 310 minutes (maximum), median 175 minutes. The median amount of blood loss was 150 mL, and hence the transfusion rate was low with only one patient requiring on-table transfusion and two patients requiring additional blood before discharge. Hospital stay ranged between 2.5 and 11 days; median postoperative stay was 3 days., Conclusions: In our initial experience, LCRN seems safe and feasible with low morbidity and a good perioperative outcome.

Introduction: To evaluate the potential and feasibility of the potassium titanyl phosphate (KTP) Greenlight laser to perform partial nephrectomy in a porcine model., Technical Considerations: A total of 15 laparoscopic partial nephrectomies were performed in 4 Danish land-raised pigs under anesthesia. Transperitoneal access was obtained, and using a total of four ports, the 80-W KTP laser was used to perform bilateral upper and lower pole partial nephrectomy. The procedures were done successfully without renal cooling or clamping of the vessels. The estimated blood loss for each procedure was less than 30 mL. Only in one operation, in which a secondary renal vein was transected, was any additional hemostasis required (a single Endoclip). The mean operating time was 42 minutes (range 31 to 59) for each partial nephrectomy. As demonstrated on video, smoke formation was, at times, a problem during the procedure, because it reduced visibility, making only intermittent application of laser energy possible. Histopathologic analysis of the specimens showed a zone of loss of substance (less than 1 mm) at the resection line and narrow adjacent zones on both sides of the resection line with minimal changes., Conclusions: We have shown for the first time that normally perfused laparoscopic partial nephrectomy using the KTP laser is feasible and efficacious in the porcine model. This represents a novel application for the KTP laser, which produced excellent renal parenchymal hemostatic ablation. We are currently working on ways to improve the visibility by reducing smoke formation before undertaking a clinical trial in humans.

Objective: To investigate the accuracy and use of body-coil magnetic resonance imaging (MRI) in the local staging of prostate cancer before radical prostatectomy (RP)., Patients and Methods: Fifty-six patients undergoing RP were staged before surgery using body-coil MRI; none was denied surgery on the basis of their scan results. All scans were reported before RP by one of three consultant radiologists and afterward by a colleague with a special interest in prostate MRI, unaware of the patients' clinical details., Results: The overall sensitivity of MRI at detecting extracapsular extension was 50% on general reporting and 72% when reported by the specialist radiologist; the respective specificities were 84% and 86%. Of the 55 patients included in the study, 18 (33%) had extracapsular disease on histological analysis. MRI was most accurate in the 17 patients at high-risk (prostate-specific antigen, PSA, >10 ng/mL and Gleason score >or= 8) and eight at intermediate risk (PSA < 10 ng/mL and Gleason score 7). In the former group with specialist analysis, the sensitivity was 100%, although this decreased to 67% with general reporting. Both gave a specificity of 82%. Intermediate risk disease gave a sensitivity and specificity of 75%, irrespective of reporting method. The ability of MRI to detect extraprostatic tumour in the 30 low-risk patients (PSA < 10 ng/mL and Gleason score 2-6) was poor; the sensitivity was 25% with general and 50% on specialist review, although both methods gave a specificity of >90%., Conclusion: Body-coil MRI is sensitive and specific for identifying extracapsular extension of prostate cancer in patients with high- or intermediate-risk disease. Patients at low risk frequently have microscopic extension which is not detected. Opinion from a radiologist with a special interest in prostate MRI can increase the reporting accuracy even when unaware of the patients' clinical details.

Purpose: We quantify and compare ultrastructural changes seen at high power on electron microscopic examination of detrusor biopsies from underactive and control bladders., Materials and Methods: The detrusor underactivity group consisted of 14 patients (mean age 64.0 years) with post-micturition residuals greater than 300 ml., impaired contractility and no obstruction on urodynamics. A total of 17 patients who voided normally voiders with residual volume less than 50 ml. served as the control group. Bladder biopsies were obtained endoscopically using cold cup technique and processed using standard methods. All specimens were randomized and studied at high power (x12,000 to x24,000) by an examiner who was blinded to the groups. All complete cells within each random grid field were counted up to a total of 500. The number of disrupted cells per 500 cells was noted., Results: Disruptive cell profiles were found in all biopsies. Median cell count was 20 cells/500 in 14 controls and 96.5 cells/500 in the underactive detrusor group (p <0.001). The number of disruptive cell profiles did not correlate with age in the control group (r = 0.34, p = 0.18)., Conclusions: There were distinct morphological changes in the detrusor associated with bladder dysfunction with approximately 4 times more disruptive cells in patients with an underactive bladder. However, there was no correlation between age and number of disruptive cells, suggesting that this is not a process of aging per se. Ultrastructure studies may have a role as an adjunct to urodynamics in the diagnosis of bladder dysfunction.

Intraoperative penile tumescence during endoscopic surgery is a troublesome complication and a challenge to the urologist. We describe a novel, convenient, safe, and readily available technique. We used an intracavernosal injection of epinephrine using a standard dental syringe and a cartridge of lidocaine 2% and epinephrine 1:80,000 to induce detumescence reliably.

Objective: To assess the 2-year symptomatic and urodynamic results of a prospective randomized trial of interstitial radiofrequency therapy of the prostate (IRFT) vs transurethral resection of the prostate (TURP)., Patients and Methods: Patients with lower urinary tract symptoms (LUTS) and urodynamic evidence of bladder outlet obstruction (BOO) were randomized to undergo IRFT or TURP and were followed up using the International Prostate Symptom Score (IPSS) and urodynamic assessment for 2 years., Results: At 2 years there was a clinically relevant reduction in the IPSS in the IRFT (20 to 9) and TURP groups (22 to 4). There was also a statistically significant reduction in the detrusor pressure at maximum urinary flow in both groups, but the reduction in the IRFT group was probably not sufficient to explain the observed symptomatic improvements solely from a reduction in BOO., Conclusion: IRFT can produce a sustained improvement in LUTS for at least 2 years. However, such improvements are unlikely to be entirely the result of a reduction in BOO. The effects of radiofrequency energy may, at least partly, be independent of any thermal effect and depend instead on neuromodulation of lower urinary tract nerves.

A radioiodinated ligand, [125I]SB-236636 [(S)-(-)3-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]3-[125I]i odo phenyl]2-ethoxy propanoic acid], which is specific for the gamma isoform of the peroxisomal proliferator activated receptor (PPARgamma), was developed. [125I]SB-236636 binds with high affinity to full-length human recombinant PPARgamma1 and to a GST (glutathione S-transferase) fusion protein containing the ligand binding domain of human PPARgamma1 (KD = 70 nM). Using this ligand, we characterized binding sites in adipose-derived cells from rat, mouse and humans. In competition experiments, rosiglitazone (BRL-49653), a potent antihyperglycemic agent, binds with high affinity to sites in intact adipocytes (IC50 = 12, 4 and 9 nM for rat, 3T3-L1 and human adipocytes, respectively). Binding affinities (IC50) of other thiazolidinediones for the ligand binding domain of PPARgamma1 were comparable with those determined in adipocytes and reflected the rank order of potencies of these agents as stimulants of glucose transport in 3T3-L1 adipocytes and antihyperglycemic agents in vivo: rosiglitazone > pioglitazone > troglitazone. Competition of [125I]SB-236636 binding was stereoselective in that the IC50 value of SB-219994, the (S)-enantiomer of an alpha-trifluoroethoxy propanoic acid insulin sensitizer, was 770-fold lower than that of SB-219993 [(R)-enantiomer] at recombinant human PPARgamma1. The higher binding affinity of SB-219994 also was evident in intact adipocytes and reflected its 100-fold greater potency as an antidiabetic agent. The results strongly suggest that the high-affinity binding site for [125I]SB-236636 in intact adipocytes is PPARgamma and that the pharmacology of insulin-sensitizer binding in rodent and human adipocytes is very similar and, moreover, predictive of antihyperglycemic activity in vivo.

A series of [(ureidoethoxy)benzyl]-2,4-thiazolidinediones and [[(heterocyclylamino)alkoxy]-benzyl]-2,4-thiazolidinediones was synthesized from the corresponding aldehydes. Compounds from the urea series, exemplified by 16, showed antihyperglycemic potency comparable with known agents of the type such as pioglitazone and troglitazone (CS-045). The benzoxazole 49, a cyclic analogue of 16, was a very potent enhancer of insulin sensitivity, and by modification of the aromatic heterocycle, an aminopyridine, 37, was identified as a lead compound from SAR studies. Evaluation of antihyperglycemic activity together with effects on blood hemoglobin content, to determine the therapeutic index, was performed in 8-day repeat administration studies in genetically obese C57 Bl/6 ob/ob mice. From these studies, BRL 49653 (37) has been selected, on the basis of antihyperglycemic potency combined with enhanced selectivity against reductions in blood hemoglobin content, for further evaluation.

A series of compounds related to ethyl 4-benzyloxybenzoate was synthesized and evaluated for potential hypolipidemic activity in rats. Structure--activity relationships are discussed in terms of cholesterol-lowering activity together with effects on weight gain and liver lipids. A number of the compounds inhibited cholesterol and free fatty acid biosynthesis from [1-14C]acetate in rat liver slices in vitro. Ethyl 4-benzyloxybenzoate, ethyl-4-benzyloxybenzoic acid, ethyl 4-p-bromobenzyloxybenzoates, and 4-o-methoxybenzyloxyphenyl acetate exhibited the most favorable spectrum of activity.

A series of analogs of N-benzylimidazole was prepared and tested for hypolipidemic activity. Both plasma cholesterol and triglyceride-lowering activity were found in several members of the series. The most active compounds were N-3-methoxy-, N-4-methoxy-, and N-4-methylbenzylimidazole. Structure-activity relationships are discussed.

The Tetronic series of polymeric surface-active agents were screened for hypocholesterolaemic activity in rats fed on a semi-synthetic hypercholesterolaemic diet. Only Tetronics 701 and 702 were active and the former was further investigated. Tetronic 701 lowered serum and liver cholesterol in rats fed on a semi-synthetic diet, with or without cholesterol, but not in rats fed on stock laboratory diet. A dose-related growth depression was observed. The compound was hypocholesterolaemic in chicks and rabbits fed on cholesterol-containing diets. The uptake of a single dose of cholesterol into liver and serum was inhibited in rats given Tetronic 701. Tetronics 701 and 702 were effective in precipitating cholesterol from mixed micelles in vitro. Non-hypocholesterolaemic Tetronics were inactive in this respect. A series of tetraesters of tetronic 701 were prepared and tested in rats fed on a semi-synthetic hypercholesterolaemic diet. Several were hypocholesterolaemic and the tetrabenzoate was of especial interest in that it depressed growth less than did Tetronic 701 itself.