A Multicenter Study of the Clinical Utility of Nontargeted Systematic Transperineal Prostate Biopsies in Patients Undergoing Pre-Biopsy Multiparametric Magnetic Resonance Imaging.

PURPOSE: The added value of nontargeted systematic prostate biopsies when performed alongside magnetic resonance imaging targeted biopsies in men referred with a suspicion of prostate cancer is unclear. We aimed to determine the clinical utility of transperineal nontargeted systematic prostate biopsies, when performed alongside targeted systematic prostate biopsies, using pre-biopsy multiparametric magnetic resonance imaging. MATERIALS AND METHODS: Consecutive patients referred with a suspicion of prostate cancer (April 2017 to October 2019) underwent pre-biopsy multiparametric magnetic resonance imaging. A transperineal biopsy was advised if multiparametric magnetic resonance imaging PI-RADS® (v.2.0) score was 4 or 5, and score 3 required a prostate specific antigen density 0.12 ng/ml or greater. Primary threshold for clinically significant prostate cancer was defined as any Gleason 3+4 or greater. Multivariable logistic regression analysis identified pre-biopsy predictors of clinically significant prostate cancer in nontargeted systematic prostate biopsies, regardless of targeted pathology (p <0.05, R, version 3.5.1). RESULTS: A total of 1,719 men underwent a pre-biopsy multiparametric magnetic resonance imaging, with 679 (39.5%) proceeding to combined targeted systematic prostate biopsies and nontargeted systematic prostate biopsies. In these men clinically significant prostate cancer was detected in 333 (49%) and 139 (20.5%) with targeted systematic prostate biopsies and nontargeted systematic prostate biopsies, respectively. In those men with clinically significant prostate cancer in targeted systematic prostate biopsies, clinically significant prostate cancer was also present in nontargeted systematic prostate biopsies in 117 (17.2%); Gleason 3+3 was present in 50 (7.4%). In 287 men without any cancer in the targeted systematic prostate biopsies, 13 (1.9%) had clinically significant prostate cancer in nontargeted systematic prostate biopsies. In addition 18/679 (2.7%) had Gleason 3+3 disease and no Gleason greater than 4+3 was detected. Predictors associated with clinically significant prostate cancer in nontargeted systematic prostate biopsies were prostate specific antigen 5 ng/ml or greater (OR 2.05, 95% CI 1.13-3.73, p=0.02), PI-RADS score 5 (OR 2.26, 95% CI 1.51-3.38, p <0.001) and prostate volume less than 50 cc (OR 2.47, 95% CI 1.57-3.87, p <0.001). CONCLUSIONS: Detection of clinically significant prostate cancer in exclusively nontargeted transperineal systematic biopsies in a pre-biopsy multiparametric magnetic resonance imaging pathway was low (1.9%).

BK Virus Associated Haemorrhagic Cystitis. A systematic review of current prevention and treatment strategies.

BACKGROUND: BK virus is a major cause of late onset haemorrhagic cystitis in patients undergoing Haematopoietic Cell Transplantation (HCT). The evidence for the management of BK Virus Associated Haemorrhagic Cystitis (BKV-HC) is limited. Much of the published data consists of non-randomised case series and case reports. To our knowledge this is the first systematic review for the management of BKV-HC in both paediatric and adult populations. Our primary outcome was to examine the evidence for strategies of 1) prevention and 2) cessation of haematuria associated with BKV. Secondary outcomes were to assess the toxicity of treatment strategies and devise management recommendations for clinicians. MATERIALS AND METHODS: We performed a systematic review of the PubMed and Central databases to evaluate the current evidence. A search protocol was prepared and registered with the PROSPERO database (CRD42017082442). The review was conducted in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement and AMSTAR (Assessing the methodological quality of systematic reviews) guidelines. Results were classified by treatment type. Qualitative analysis of included articles was performed, and grades of recommendations were devised for each treatment. RESULTS: Of 896 titles screened, 44 articles were included for qualitative analysis. The overall quality of evidence was low. There is insufficient evidence to recommend prophylactic quinolones. 40 studies evaluated treatments for established BKV-HC. There are no high-quality comparative studies. Cidofovir is the most studied treatment but quality of evidence is low, and grade of recommendation is weak. Hyperbaric oxygen therapy, Fibrin glue, Leflunomide, Sodium Pentosan Polysulfate, Intravesical Alum and Radiological embolisation have all been described but the effectiveness of these treatments is unclear. CONCLUSION: There remains no clear specific treatment for BKV-HC. An effective multi-disciplinary approach leading to early recognition and initiation of treatment is encouraged. The development of novel therapies followed by well-designed clinical studies are urgently needed.

A prospective clinical, cost and environmental analysis of a clinician-led virtual urology clinic.

INTRODUCTION: A virtual clinic is a form of telemedicine where contact between clinical teams and patients occur without face-to-face consultation. Our study aims to quantify the clinical, financial and environmental benefits of our virtual urology clinic. MATERIAL AND METHODS: We collected data prospectively from our weekly follow-up virtual clinic over a continuous four-month period between July and September 2017. RESULTS: In total, we reviewed 409 patients. Following virtual clinic consultation, 68.5% of our patients were discharged from further follow-up. The majority of our patients (male 57.7%, female 55.5%) were of working age. The satisfaction scores were high, at 90.1%, and there were no reported adverse events as a result of using the virtual clinic. Our calculated cost savings were £18,744, with a predicted 12-month cost saving of £56,232. The creation of additional face-to-face clinic capacity has created an estimated 12-month increase in tariff generation for our unit of £72,072. In total, 4623 travel miles were avoided by patients using the virtual clinic, with an estimated avoided carbon footprint of 0.35-1.45 metric tonnes of CO2e, depending on mode of transport. Our predicted 12-month avoided carbon footprint is 1.04-4.04 metric tonnes of CO2e. CONCLUSIONS: Our virtual clinic model has demonstrated a trifecta of positive outcomes, namely, clinical, financial and environmental benefits. The environmental importance and benefits of a virtual clinic should be promoted as a social enterprise value when engaging stakeholders in setting up such a urological service. We propose the adoption of our virtual clinic model in those urological units considering this method of telemedicine.

Case report: delayed hemorrhage from an accessory internal pudendal artery pseudoaneurysm after robotic radical prostatectomy: successful management with ct angiography and embolization.

We present the first report of a pseudoaneurysm of an accessory internal pudendal artery after transperitoneal robotic radical prostatectomy. The vesicourethral anastomosis was performed using two continuous 3-0 Monocryl sutures tied at the six o'clock position. As the anastomotic suture was placed at 11 o'clock, lateral to the dorsal venous complex, there was a small amount of pulsatile bleeding that ceased when the suture was completed and tied. The lesion presented as hematuria beginning on the fourth day. On the 14(th) day, the pseudoaneurysm was diagnosed by CT angiography and treated by embolization with eight 3-mm/30-mm micro coils after superselective catheterization. There were no complications or further hematuria.

Report of laparoscopic ureteropyelostomy for symptomatic "yo-yo" reflux in an adult.

Symptomatic presentation of partial duplication of the ureter in adults is rare. However, there are reports of such conditions being treated with surgical correction with varying degrees of success. We present the case of a 23-year-old woman who underwent what is, to our knowledge, the first reported laparoscopic ureteropyelostomy for symptomatic "yo-yo" reflux.

Robotic prostatectomy: the first UK experience.

BACKGROUND: We describe a teamwork approach to setting up the UK's first clinical programme for robotically assisted laparoscopic radical prostatectomy. METHODS: On 22 November 2004 the Imperial Robotic Urological Surgery Group performed their first robotically assisted prostatectomy. Robotically assisted prostatectomy lends itself to division into eight definable stages. A team of four consultant urological surgeons utilized a structured rotating system, using these stages, for time at the console and tableside assisting. Fluidity of surgery was maintained by a surgeon acting as the tableside assistant for the stage prior to moving to the console. Data was collected prospectively for the first 50 cases and parameters associated with the learning curve compared to other reported series. RESULTS: Median operative time of 369.5 mins, median blood loss of 700 ml, with 12% of patients requiring a blood transfusion. Four patients required conversion to an open procedure; one resulting from equipment failure and three due to failure of progression. Four patients had an anastomotic leak with resulting ileus and two patients sustained rectal injuries, which were repaired intraoperatively using the robot. Median hospital stay was 4 days with a 22% positive surgical margin rate. CONCLUSION: Parameters indicative of the learning curve are comparable to existing published initial series of other robotic centres. The use of teamwork has enabled us to provide safe and time-efficient training for four surgeons simultaneously. The structured approach used in this setting demonstrates that urological surgeons of varying laparoscopic experience can acquire the skills necessary to competently perform laparoscopic radical prostatectomy.

Endopyelotomy in the symptomatic older child.

OBJECTIVE: To evaluate the results of endopyelotomy in children, an established method in adult practice as a treatment for pelvi-ureteric junction (PUJ) obstruction. PATIENTS AND METHODS: Endopyelotomies undertaken between 1992 and 1999 by one surgeon in an established endourology unit were reviewed retrospectively. Children aged > 5 years presenting with pain and obstruction on isotope renography were selected for endopyelotomy. Patients with crossing vessels detectable on spiral computed tomography were treated by open pyeloplasty. Access to the renal pelvis was provided by a uroradiologist. Endopyelotomy was carried out through an Amplatz sheath of (median) 26 F. After applying traction to invaginate the PUJ an incision was made postero-laterally using electrocautery via an 11 F paediatric resectoscope. Stenting was maintained for 6 weeks. In all, 13 patients (median age 10 years, range 5-14) were treated; two had associated calculi. RESULTS: The symptoms resolved and the obstruction was relieved in only six patients, with a median (range) follow-up of 50 (26-68) months. The seven patients in whom endopyelotomy failed, as indicated by persistent pain, proceeded to open pyeloplasty at a median (range) of 4 (1.3-79) months. Of these, two had presented with associated multiple calculi and significant hydronephrosis (one with an associated duplex system) and three had crossing lower pole vessels at open operation. One developed a urinoma after the original endopyelotomy and one had a retained stent fragment removed at the time of pyeloplasty. CONCLUSIONS: Endopyelotomy in the symptomatic child requires a careful preoperative evaluation. Crossing lower pole vessels warrant an open pyeloplasty.

Allogeneic whole-tumour cell vaccination in the rat model of prostate cancer.

OBJECTIVE: To investigate cancer immunotherapy using whole allogeneic (differing tissue-type) tumour cells as vaccines in the rat prostate cancer model. Materials and methods Two rat models of prostate cancer were used; MAT-LyLu tumours which grow in Copenhagen rats and PAIII tumours which grow in Lobund-Wistar rats, with crossover of the cell lines to test allogeneic vaccination. The cell lines were immunologically characterized by flow cytometry. Irradiated tumour cells were administered as subcutaneous vaccines either before tumour challenge or after tumour establishment (both subcutaneous). A preparation of heat-killed Mycobacterium vaccae bacilli (SRL172) was used as an adjuvant to increase vaccine efficiency. RESULTS: Flow cytometry analysis of the cell lines showed that the PAIII cells had higher levels of major histocompatibility complex (MHC) class I and intercellular adhesion molecule (ICAM-1) expression than the MAT-LyLu cells. However, both tumour cell lines were rejected in their allogeneic hosts. Prophylactic vaccination with allogeneic MAT-LyLu cells protected against PAIII tumour challenge in Lobund-Wistar rats, with 80% of animals surviving for > 5 months, compared with 40% for animals receiving autologous cells. The immunity was prolonged, as rats were protected when rechallenged 5 months later. In Copenhagen rats allogeneic PAIII cells protected against the more aggressive MAT-LyLu tumour challenge only when the cells were combined with SRL172. Initial therapy experiments showed that vaccination with the cell lines mediated only limited tumour regression in the Lobund-Wistar rats. CONCLUSION: The allogeneic tumour cell vaccination model described is valuable for assessing the principle and efficacy of allogeneic prostate cancer cell vaccines for clinical use.

The immunotherapy of prostate cancer.

Advanced prostate cancer remains incurable with standard treatment options. Immunotherapy may be a realistic alternative given the growing evidence that the immune response can affect the growth of other solid tumours and the regulation of both specific and shared prostate cancer antigens. Early studies suggest that both non-specific and specific vaccines can effect relevant animal models and clinical trials based on these observations are now in progress. A number of other approaches including gene therapy with HSVtk are already undergoing clinical studies (Herman et al. Hum Gene Ther 1999; 10: 1239-1249). Prostate Cancer and Prostatic Diseases (2000) 3, 303-307

Gene therapy for prostate cancer.

Prostate cancer is one of the leading causes of cancer deaths in the western hemisphere. A number of different gene therapy strategies are currently being evaluated. The ex vivo and many of the in vivo therapies involve stimulating a specific antitumor immune response. Autologous vaccines involving interleukin-2 (IL-2)- or granulocyte-macrophage colony-stimulating factor (GM-CSF)-transduced whole tumor cells showed great promise in animal models. Clinical trials of these and other vaccine strategies are underway. In vivo gene therapies involving the replacement of mutant tumor-suppressor genes, antisense strategies, and the insertion of suicide genes are also being evaluated in prostate cancer.

Immunotherapy of advanced prostate cancer: a phase I/II trial using Mycobacterium vaccae (SRL172).

OBJECTIVE: To assess whether a new heat-killed Mycobacterium vaccae preparation (SRL172), which enhances cell-mediated immunity and has been proposed for use as an immunotherapeutic agent against cancer, is safe in patients with advanced hormone-refractory prostate cancer, can stimulate desirable cytokine changes in these patients and modulate the progression of the disease. PATIENTS AND METHODS: Ten patients were given SRL172 intradermally at regular intervals. The serum prostate specific antigen (PSA) level was used as a surrogate marker of response. The proportion of peripheral blood mononuclear cells (PBMC) secreting interleukin 2 (IL2), interferon gamma (IFNgamma) and interleukin 4 (IL4) was measured by flow cytometry (FACS) before and after vaccination to assess whether the treatment induced a Th2 (predominantly humoral) to Th1 (predominantly cell-mediated) switch. RESULTS: There were no significant adverse events. In five patients the serum PSA declined during the trial and in two of these there was no concomitant change of therapy apart from vaccination with SRL172. Before vaccination with SRL172 patients had a low proportion of PBMC producing IFNgamma and IL2 (all 10) and a higher proportion secreting IL4 (all three tested), suggesting a predominantly Th2 cytokine profile. After vaccination the proportion of IL4 secreting PBMC fell in all three patients tested. The proportion of IL2 secreting PBMC increased in three patients whose PSA fell. The proportion of IFNgamma-secreting cells remained depressed in nine of 10 patients. CONCLUSION: Two patients with advanced hormone-refractory prostate cancer had a PSA response to the vaccination with SRL172. The proportion of PBMC secreting IL2 is a potential marker of response to immunotherapy.

Mycobacterium vaccae (SRL172): a potential immunological adjuvant evaluated in rat prostate cancer.

OBJECTIVE: To evaluate the potential of heat-killed Mycobacterium vaccae (SRL172) as a nonspecific immunostimulant and as an adjuvant to whole tumour cell vaccination in the rat model of prostate cancer. MATERIALS AND METHODS: SRL172 was used as a vaccine in the prevention and treatment of subcutaneous tumours in rats. Prevention experiments were conducted using subcutaneous MAT-LyLu tumours in Copenhagen rats, comparing vaccination with SRL172 alone, SRL172 plus autologous cells, and bacille Calmette-Guèrin (BCG) plus autologous cells before tumour implantation. Treatment experiments were conducted using subcutaneous MAT-LyLu tumours in the Copenhagen rat and subcutaneous PAIII tumours in the Lobund-Wistar rat. Tumours were induced by subcutaneous injection with tumour cells. Animals were then vaccinated with autologous cells, autologous cells plus SRL172, or SRL172 alone. RESULTS: SRL172 was effective as an adjuvant to autologous whole tumour cell vaccination in the prevention of MAT-LyLu tumours and the survival benefit was equivalent to that provided when the adjuvant was live-attenuated BCG. SRL172 alone did not reduce tumour take or tumour growth in this model and neither strategy was effective in delaying the growth of established MAT-LyLu tumours. In the Lobund-Wistar rat vaccination with autologous whole tumour cells and SRL172 significantly delayed the growth of established tumours. CONCLUSION: Mycobacterium vaccae deserves further evaluation as an adjuvant to whole tumour cell vaccination in a phase I clinical trial in patients with prostate cancer.

Multiple frequent recurrences in superficial transitional cell carcinoma of the bladder: is survival compromised by a conservative management strategy?

OBJECTIVE: To examine whether a strategy of bladder conservation is reasonable in patients with multiple frequent superficial recurrences of transitional cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: Fifty-four patients with pTa/pT1. G1/G2 tumours at diagnosis, with five or more recurrences at two or more cystoscopies within 2 years of diagnosis and a minimum follow-up of 4 years were identified. The patients were categorized according to outcome, i.e. disease settled, continuing high-activity disease and disease progression. RESULTS: Forty-four patients did not progress, of whom 16 continued to have high-activity disease and 28 settled to a lower disease activity. One patient had a cystectomy for superficial disease. Nine patients progressed, six with muscle invasion in the bladder and three elsewhere in the urinary tract. Neither grade nor stage were predictive of recurrence. All but one of the patients with progression had both multicentric tumours at diagnosis and a positive cystoscopy at 3 months. Three patients died from their bladder cancer. CONCLUSION: A policy of endoscopic resections and intravesical chemotherapy or bacille-Calmette-Guèrin, with cystectomy reserved until muscle-invasive disease develops, does not significantly compromise survival in patients with high-activity superficial TCC. Cystectomy for superficial disease is rarely necessary.

Written consent is haphazard for minor urological procedures.

OBJECTIVE: To determine the current practice among British urologists for obtaining written consent for flexible cystoscopy and other minor procedures under local anaesthesia. METHODS: Postal questionnaires were sent to full members of The British Association of Urological Surgeons practising in the UK asking if they obtained written informed consent for local anesthetic procedures, e.g. flexible cystoscopy, urethral dilatation, and urethral catheterization for retention, for urodynamics or for intravesical chemotherapy. They were also asked whether they recorded that the risks and benefits of the procedure had been explained to the patient. RESULTS: Respondents were divided on whether they obtained written consent for flexible cystoscopy and urethral dilatation. Most did not obtain written consent for catheterization for retention, urodynamics, intravesical chemotherapy or suprapubic catheterization. The policy was inconsistent both between and within urologists. CONCLUSION: Given the medicolegal importance of informed consent, consensus among urologists is required so that national guidelines can be developed and a more rational policy applied.