Regional Histopathology and Prostate MRI Positivity: A Secondary Analysis of the PROMIS Trial.

Background The effects of regional histopathologic changes on prostate MRI scans have not been accurately quantified in men with an elevated prostate-specific antigen (PSA) level and no previous biopsy. Purpose To assess how Gleason grade, maximum cancer core length (MCCL), inflammation, prostatic intraepithelial neoplasia (PIN), or atypical small acinar proliferation within a Barzell zone affects the odds of MRI visibility. Materials and Methods In this secondary analysis of the Prostate MRI Imaging Study (PROMIS; May 2012 to November 2015), consecutive participants who underwent multiparametric MRI followed by a combined biopsy, including 5-mm transperineal mapping (TPM), were evaluated. TPM pathologic findings were reported at the whole-prostate level and for each of 20 Barzell zones per prostate. An expert panel blinded to the pathologic findings reviewed MRI scans and declared which Barzell areas spanned Likert score 3-5 lesions. The relationship of Gleason grade and MCCL to zonal MRI outcome (visible vs nonvisible) was assessed using generalized linear mixed-effects models with random intercepts for individual participants. Inflammation, PIN, and atypical small acinar proliferation were similarly assessed in men who had negative TPM results. Results Overall, 161 men (median age, 62 years [IQR, 11 years]) were evaluated and 3179 Barzell zones were assigned MRI status. Compared with benign areas, the odds of MRI visibility were higher when a zone contained cancer with a Gleason score of 3+4 (odds ratio [OR], 3.1; 95% CI: 1.9, 4.9; P < .001) or Gleason score greater than or equal to 4+3 (OR, 8.7; 95% CI: 4.5, 17.0; P < .001). MCCL also determined visibility (OR, 1.24 per millimeter increase; 95% CI: 1.15, 1.33; P < .001), but odds were lower with each prostate volume doubling (OR, 0.7; 95% CI: 0.5, 0.9). In men who were TPM-negative, the presence of PIN increased the odds of zonal visibility (OR, 3.7; 95% CI: 1.5, 9.1; P = .004). Conclusion An incremental relationship between cancer burden and prostate MRI visibility was observed. Prostatic intraepithelial neoplasia contributed to false-positive MRI findings. ClinicalTrials.gov registration no. NCT01292291 © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Harmath in this issue.

Outcomes and Long-term Follow-up of Patients with Cystine Stones: a Systematic Review.

PURPOSE OF REVIEW: Cystine stone patients can be difficult to manage with frequent recurrences. We performed a systematic review with a view to assessing interventions, compliance and their long-term outcomes. RECENT FINDINGS: Ten retrospective observational studies (253 patients) assessed the outcomes and long-term follow-up of cystine stone patients. The mean length of follow-up was 9.6 years (range 3.5-21.8 years). The overall mean number of surgical procedures/patient was 5.7 (range 2-9.8/patient) with the overall mean number of surgical procedures/patient/year at 0.59 (range 0.22-1.32/patient/year). While open surgery has decreased over the last decade and PCNL has been stable, there seems to be a rise of RIRS during this period. Patients with cystine stones need periodic interventions for stone recurrences despite medical management, with limited data showing the impact on renal function. While the management is individualised, wide variability exists with often poor and incomplete patient data.

Safety and efficacy of Holmium laser enucleation of the prostate (HoLEP) in patients with previous transperineal biopsy (TPB): outcomes from a dual-centre case-control study.

BACKGROUND: We investigated the surgical feasibility, safety and effectiveness of 50 W (low power) Holmium Laser enucleation of the prostate (HoLEP) in patients who have undergone previous template biopsy of the prostate (TPB). METHODS: Data encompassing pre-operative baseline characteristics, intra-operative measures and post-operative outcomes was collected for 109 patients undergoing HoLEP across two UK centres. Patients were stratified into two groups; group 1 (n = 24) had undergone previous TPB were compared with 'controls' (no previous TPB) in group 2 (n = 85). The primary outcome was successful HoLEP. RESULTS: There were no statistically significant differences in either key baseline characteristics or mass of prostate enucleated between groups 1 and 2. There was no statistically significant difference in enucleation or morcellation times parameters between the two groups other than enucleation efficiency in favour of group 1 (p = 0.024). Functional outcomes improved, without any statistically significant difference, in both groups. CONCLUSIONS: In patients with a previous TPB, HoLEP is surgically feasible, safe and effective. TPB should not be considered a contraindication to HoLEP. Our work provides a strong foundation for further research in this area.

False Positive Multiparametric Magnetic Resonance Imaging Phenotypes in the Biopsy-naïve Prostate: Are They Distinct from Significant Cancer-associated Lesions? Lessons from PROMIS.

BACKGROUND: False positive multiparametric magnetic resonance imaging (mpMRI) phenotypes prompt unnecessary biopsies. The Prostate MRI Imaging Study (PROMIS) provides a unique opportunity to explore such phenotypes in biopsy-naïve men with raised prostate-specific antigen (PSA) and suspected cancer. OBJECTIVE: To compare mpMRI lesions in men with/without significant cancer on transperineal mapping biopsy (TPM). DESIGN, SETTING, AND PARTICIPANTS: PROMIS participants (n=235) underwent mpMRI followed by a combined biopsy procedure at University College London Hospital, including 5-mm TPM as the reference standard. Patients were divided into four mutually exclusive groups according to TPM findings: (1) no cancer, (2) insignificant cancer, (3) definition 2 significant cancer (Gleason ≥3+4 of any length and/or maximum cancer core length ≥4mm of any grade), and (4) definition 1 significant cancer (Gleason ≥4+3 of any length and/or maximum cancer core length ≥6mm of any grade). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Index and/or additional lesions present in 178 participants were compared between TPM groups in terms of number, conspicuity, volume, location, and radiological characteristics. RESULTS AND LIMITATIONS: Most lesions were located in the peripheral zone. More men with significant cancer had two or more lesions than those without significant disease (67% vs 37%; p< 0.001). In the former group, index lesions were larger (mean volume 0.68 vs 0.50 ml; p< 0.001, Wilcoxon test), more conspicuous (Likert 4-5: 79% vs 22%; p< 0.001), and diffusion restricted (mean apparent diffusion coefficient [ADC]: 0.73 vs 0.86; p< 0.001, Wilcoxon test). In men with Likert 3 index lesions, log2PSA density and index lesion ADC were significant predictors of definition 1/2 disease in a logistic regression model (mean cross-validated area under the receiver-operator characteristic curve: 0.77 [95% confidence interval: 0.67-0.87]). CONCLUSIONS: Significant cancer-associated MRI lesions in biopsy-naïve men have clinical-radiological differences, with lesions seen in prostates without significant disease. MRI-calculated PSA density and ADC could predict significant cancer in those with indeterminate MRI phenotypes. PATIENT SUMMARY: Magnetic resonance imaging (MRI) lesions that mimic prostate cancer but are, in fact, benign prompt unnecessary biopsies in thousands of men with raised prostate-specific antigen. In this study we found that, on closer look, such false positive lesions have different features from cancerous ones. This means that doctors could potentially develop better tools to identify cancer on MRI and spare some patients from unnecessary biopsies.

Incidental urinary tract pathologies in the one-stop prostate cancer clinic.

OBJECTIVE: We determined the prevalence of incidental urinary tract pathologies in patients referred to the one-stop suspected prostate cancer clinic and assessed the evaluation and outcome of these pathologies. METHODS: One hundred and ninety patients were referred to the one-stop suspected prostate cancer clinic over a 6-month period. The records of patients with incidental urinary tract pathologies were retrospectively reviewed for demographic characteristics, mode of clinical presentation, further investigations performed, the final diagnosis and the treatment given. RESULTS: Incidental urinary tract pathologies were detected in 12 patients (6.3%). Clinically significant pathologies were found in 4.7% patients (n = 9). Significant incidental findings included bladder cancers (n = 8) and renal cell carcinoma (n = 1). All of these patients had additional diagnostic investigations, required in-patient surgical treatment and have remained disease free at follow up. Trans-rectal ultrasound guided prostate biopsies were only performed in three cases and a diagnosis of prostate cancer was only made in one patient. CONCLUSION: Incidental urinary tract pathologies among patients referred to the one-stop suspected prostate cancer clinic are common. This reflects the need for further investigating patients with lower urinary tract symptoms whenever necessary so avoid missing significant pathologies.

What Type of Prostate Cancer Is Systematically Overlooked by Multiparametric Magnetic Resonance Imaging? An Analysis from the PROMIS Cohort.

BACKGROUND: All risk stratification strategies in cancer overlook a spectrum of disease. The Prostate MR Imaging Study (PROMIS) provides a unique opportunity to explore cancers that are overlooked by multiparametric magnetic resonance imaging (mpMRI). OBJECTIVE: To summarise attributes of cancers that are systematically overlooked by mpMRI. DESIGN, SETTING, AND PARTICIPANTS: PROMIS tested performance of mpMRI and transrectal ultrasonography (TRUS)-guided biopsy, using 5 mm template mapping (TPM) biopsy as the reference standard. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were overall and maximum Gleason scores, maximum cancer core length (MCCL), and prostate-specific antigen density (PSAD). Cancer attributes were compared between cancers that were overlooked and those that were detected. RESULTS AND LIMITATIONS: Of men with cancer, 7% (17/230; 95% confidence interval [CI] 4.4-12%) had significant disease overlooked by mpMRI according to definition 1 (Gleason ≥ 4 + 3 of any length or MCCL ≥ 6 mm of any grade) and 13% (44/331; 95% CI 9.8-17%) according to definition 2 (Gleason ≥ 3 + 4 of any length or MCCL ≥ 4 mm). In comparison, TRUS-guided biopsy overlooked 52% (119/230; 95% CI 45-58%) of significant disease by definition 1 and 40% (132/331; 95% CI 35-45%) by definition 2. Prostate cancers undetected by mpMRI had significantly lower overall and maximum Gleason scores (p = 0.0007; p < 0.0001) and shorter MCCL (median difference: 3 mm [5 vs 8 mm], p < 0.0001; 95% CI 1-3) than cancers that were detected. No tumours with overall Gleason score > 3 + 4 (Gleason Grade Groups 3-5; 95% CI 0-6.4%) or maximum Gleason score > 4 + 3 (Gleason Grade Groups 4-5; 95% CI 0-8.0%) on TPM biopsy were undetected by mpMRI. Application of a PSAD threshold of 0.15 reduced the proportion of men with undetected cancer to 5% (12/230; 95% CI 2.7-8.9%) for definition 1 and 9% (30/331; 95% CI 6.2-13%) for definition 2. Application of a PSAD threshold of 0.10 reduced the proportion of men with undetected disease to 3% (6/230; 95% CI 1.0-5.6%) for definition 1 cancer and to 3% (11/331; 95% CI 1.7-5.9%) for definition 2 cancer. Limitations were post hoc analysis and uncertain significance of undetected lesions. CONCLUSIONS: Overall, a small proportion of cancers are overlooked by mpMRI, with estimates ranging from 4.4% (lower boundary of 95% CI for definition 1) to 17% (upper boundary of 95% CI for definition 2). Prostate cancers undetected by mpMRI are of lower grade and shorter length than cancers that are detected. PATIENT SUMMARY: Prostate cancers that are undetected by magnetic resonance imaging (MRI) are smaller and less aggressive than those that are detected, and none of the most aggressive cancers are overlooked by MRI.

A new model for suprapubic catheterization: the MediPlus Seldinger suprapubic catheter.

Insertion of a suprapubic catheter is one of the essential skills that all surgeons should master. It provides an alternative way to drain the bladder in cases where urethral catheterization is contraindicated or deemed difficult. It also has a role in elective cases where long-term drainage of the bladder is required. In this article, we discuss the MediPlus suprapubic catheter kit, which offers a new and potentially promising technique for safe introduction of the catheter into the bladder.

Prolonged and Increased Usage of a Flexible Ureterorenoscope: The Maelor FURS Protocol.

We present our point of technique detailing the specific preoperative and postoperative steps used in our institution to prolong the use of a flexible ureterorenoscope, and discuss the potential cost-effectiveness of this protocol. We have used a single flexible ureterorenoscope, for 145 consecutive cases to date, using the protocol described in this article. This prolonged use has resulted in a calculated cost per case of £273.48 GBP. We have described our experience of a dedicated protocol to prolong the usage of a single flexible ureterorenoscope. We would consider recommending the technique described in this article, to prolong flexible ureterorenoscope usage in a cost-effective manner.

Percutaneous needle biopsy for indeterminate renal masses: a national survey of UK consultant urologists.

BACKGROUND: The use of percutaneous needle biopsy in the evaluation of indeterminate renal masses is controversial and its role in management remains largely unclear. We set to establish current practice on this issue in UK urology departments. METHODS: We conducted a national questionnaire survey of all consultant urologists in the UK, to establish current practice and attitudes towards percutaneous needle biopsy in the management of indeterminate renal masses. RESULTS: 139 (43%) consultant urologists never use biopsy, whereas 111 (34%) always employ it for the diagnosis of indeterminate renal masses. 75 (23%) urologists use biopsy only for a selected patient group. Mass in a solitary kidney, bilateral renal masses and a past history of non-renal cancer were the main indications for use of percutaneous biopsy. The risk of false negative results and biopsy not changing the eventual management of their patients were the commonest reasons not to perform biopsy. CONCLUSION: There is a wide and varied practice amongst UK Consultant Urologists in the use of percutaneous biopsy as part of the management of indeterminate renal masses. The majority of urologists believe biopsy confers no benefit. However there is a need to clarify this issue in the wake of recent published evidence as biopsy results may provide critical information for patients with renal masses in a significant majority. It not only differentiates benign from malignant tissue but can also help in deciding the management option for patients undergoing minimally invasive treatments.

Long-term follow-up after retroperitoneal laparoscopic decortication of symptomatic renal cysts.

INTRODUCTION: The purpose of this study was to present our long-term experience of retroperitoneal laparoscopic decortication (RLD) for patients with severely symptomatic simple renal cysts. The feasibility, safety and efficacy of this technique is reported, along with immediate and long-term clinical outcomes. MATERIALS AND METHODS: Over a 6-year period, 22 consecutive patients with symptomatic simple renal cysts underwent RLD by a single surgeon. Demographic data, perioperative blood loss, length of operative procedure, length of hospital stay and complications were analyzed. Follow-up included clinical review and renal ultrasonography, at 6-monthly intervals for 1 year, and then annually. RESULTS: The mean patient age was 45 (range 31-63) years. RLD was successfully performed in all 22 patients - no open conversions were required. There was no mortality and there were no perioperative complications. Mean duration of surgery was 101.9 min (59-117 min) and operative blood loss was <150 ml in all cases (10-150 ml). Mean length of hospital stay was 3.2 (2-6) days and return to normal activities was achieved after a mean of 15 (10-30) days. At a mean follow-up of 60 (22-93) months, 17 patients (77%) were completely relieved of symptoms, while 5 (23%) patients complained of some pain not requiring any analgesia. Renal ultrasonography showed an absence of radiological recurrence of the symptomatic renal cyst in all cases. CONCLUSION: RLD is a safe and effective method to treat symptomatic renal cysts, with an immediate postoperative symptomatic relief, a short convalescence period and effective 5-year clinical and radiological outcome.

The artificial urinary sphincter.

Urinary incontinence (UI) is regarded as a major health issue affecting a large sector of the population. The International Continence Society defines UI as the complaint of involuntary leakage of urine that is objectively demonstrated and is a social and hygienic problem. It is caused by a wide range of factors and it has a great negative impact on the lifestyle of patients, as well as a burden on the healthcare system, since it affects an estimated 10 million patients in the USA. Approximately 50% of all nursing home residents and between 15 and 30% of women over the age of 65 years have UI. The treatment modalities vary according to the underlying causes and the results are often unsatisfactory. With the introduction of the artificial urinary sphincter there has been a dramatic change in the management of refractory cases of UI. The artificial urinary sphincter is a device, usually in the form of an inflatable silicone cuff, inserted around the bladder neck or around the bulbous urethra in adult males. It mimics the biological urinary sphincter by providing a competent bladder outlet during urinary storage and an open outlet to permit voluntary voiding. In this review we give an overview of UI and the artificial urinary sphincter as a method of treatment.

Greenlight prostatectomy: a challenge to the gold standard? A review of KTP photoselective vaporization of the prostate.

The use of lasers to carry out resection of the prostate gland is an ever-evolving field which has seen several different modalities of laser light used with varying success. This review looks at what makes the traditional transurethral resection of prostate the gold standard and provides the evidence on the evolution of the laser prostatectomy in trying to usurp it as the favored procedure for symptomatic benign prostatic hyperplasia. In particular, we show how the latest laser technology in the form of the Greenlight laser is challenging not only other lasers such as the holmium laser, but may form a strong contender to replace the transurethral resection of prostate.

Urolift - minimally invasive surgical BPH management.

INTRODUCTION: An ideal treatment option for symptomatic Benign Prostatic Hyperplasia (BPH) should relieve lower urinary tract symptoms (LUTS) and restore Quality of Life (QoL). Currently available medical therapies and surgical options for symptomatic BPH have side effects that adversely affects quality of life. Prostatic urethral lift (PUL) is a novel endourology procedure that promises to relieve LUTS without the aforementioned side effects. Areas covered: We diligently reviewed all the published literature on PUL, till July 2016 using standard search criteria. Expert commentary: There is good quality evidence to establish the efficiency of PUL in treating symptomatic BPH without adversely affecting the QoL. Based on the current literature, PUL can be considered as an option for those symptomatic BPH patients with small or medium size prostates (< 80 ml) without median lobe enlargement, who failed on medical therapy or are intolerant to it and wish to preserve their sexual function.

The Use of Cook Resonance Metallic Ureteral Stent in Cases of Obstructive Uropathy from Persistent Neoureteral Stenosis, Following Kidney Transplantation.

Introduction: Following kidney transplantation, persistent cases of obstructive uropathy from neoureteral stenosis, at the reimplantation site, may require management with permanent, long-term Double-J stenting, following failed open surgical and minimally invasive procedures. We report our experience of the use of Cook Resonance® metallic ureteral stent to manage such cases endourologically. Materials and Methods: Medium-term follow-up of two cases requiring long-term ureteral stenting. Medical records, operative details, and radiologic data were reviewed. Primary outcome was relief of obstructive uropathy, and secondary outcomes included clinicoradiologic complications and cost-effectiveness of the metallic stents compared with standard Double-J stents. Results: Case 1 was a 45-year-old lady with obstructive uropathy after kidney transplantation. To date, she has had four metallic stents, and on review of operative details and radiologic data, there was seen to be a 60% reduction in operation length from the first to fourth stent exchange. Radiation dose exposure saw an 80% reduction from 2852 to 556 CGy·cm2. Following 3 years of follow-up, relief of obstructive uropathy has been maintained, with no radiologic or clinical evidence of complications. Case 2 was a 44-year-old lady with obstructive nephropathy requiring long-term stenting after kidney transplantation. Two stent exchanges have been performed to date with a 38% reduction in operation length from 50 minutes to just 31 minutes. Radiation dose exposure saw a 41% reduction. No clinicoradiologic complications or stent-related symptoms have occurred. Discussion: In our experience, use of metallic stents in transplanted kidneys is safe and feasible, with both patients having effective and sustained relief of obstructive uropathy. This stent appears to be well tolerated and is associated with minimal clinicoradiologic complications. Metallic stent replacement is also cost-effective due to the fact that it only requires annual rather than 6-monthly stent changes.

The metastatic cascade in prostate cancer.

Morbidity and mortality due to prostate cancer are mainly a result of prostate cancer metastases. After the initial neoplastic transformation of cells, the process of metastasis involves a series of sequential steps, which involve neoangiogenesis and lymphangiogenesis, loss of adhesion with migration away from the primary tumour and entry into the systemic vasculature or lymphatics. Metastatic growth in sites such as lymph nodes and bone marrow then involves the specific non-random homing of prostate cancer cells. An appreciation and understanding of this metastatic cascade in relation to prostate cancer is clinically important in order to stratify men with prostate cancer into prognostic groups. Moreover, it is crucial in the future development of therapies that can prevent metastases.

Basic principles of real-time quantitative PCR.

Real-time quantitative PCR allows the sensitive, specific and reproducible quantitation of nucleic acids. Since its introduction, real-time quantitative PCR has revolutionized the field of molecular diagnostics and the technique is being used in a rapidly expanding number of applications. This exciting technology has enabled the shift of molecular diagnostics toward a high-throughput, automated technology with lower turnaround times. This article reviews the basic principles of real-time PCR and describes the various chemistries available: the double-stranded DNA-intercalating agent SYBR Green 1, hydrolysis probes, dual hybridization probes, molecular beacons and scorpion probes. Quantitation methods are discussed in addition to the competing instruments available on the market. Examples of applications of this important and versatile technique are provided throughout the review.

Autonomic dysreflexia: the forgotten medical emergency.

Autonomic dysreflexia (AD) is a potentially dangerous complication of spinal cord injury (SCI). In AD, an individual's blood pressure may rise to dangerous levels and, if not treated, can lead to stroke and possibly death. All medical personnel, especially those interacting with SCI patients, must have a good understanding of its aetiology, complications and emergency management.

Tissue microarrays: a current medical research tool.

Recent research in molecular biology has identified a significant number of novel markers, which may have diagnostic, prognostic and therapeutic significance. This is particularly pertinent in the field of cancer. Validation of these markers in multiple clinical specimens is currently performed by traditional histopathological techniques, which are disappointingly time consuming, labour intensive and, therefore, economically costly. These limitations have hampered the introduction of many novel markers into everyday clinical practice. The tissue microarray (TMA) is a high throughput technique, which allows the rapid and cost effective validation of novel markers in multiple pathological tissue specimens. Tissue from up to a 1000 histology blocks can be arrayed accurately onto a newly created paraffin block, at designated locations. Subsequently, morphological and molecular investigations can be performed to determine the clinical significance of the novel markers tested. It is now firmly established that the TMA can significantly accelerate the processing of a very large number of tissue specimens with excellent quality, good reliability and preservation of original tissue, with ultimate clinical benefit.

Luteinising hormone releasing hormone analogues in the treatment of prostate cancer.

The use of the luteinising hormone releasing hormone (LHRH) analogues--goserelin (Zoladex, AstraZeneca) and leuprorelin (Prostap, Wyeth)--is well established and forms the backbone of the treatment of locally advanced and metastatic prostate cancer. Comparable efficacy with orchidectomy and, historically, diethylstilbestrol (DES) is accepted, with the advantages of reversibility and limited thromboembolic and cardiovascular toxicity, respectively. Side effects such as hot flushes, loss of libido, lethargy and decreased bone mineral density have recently stimulated more interest in the use of non-steroidal anti-androgens such as bicalutamide (Casodex, AstraZeneca) in locally advanced disease. Although better tolerated, bicalutamide has significant problems with gynaecomastia and breast pain. Maximal androgen blockade using LHRH analogues and their adjuvant use with radiotherapy are discussed, as well as their experimental application in intermittent androgen suppression therapy. Similar side effect profiles are reported for the LHRH analogues but injection tolerability differs with the smaller 23G needle for Prostap 3 compared to the 16G needle for Zoladex LA. There is no evidence to suggest a difference in the efficacy between the LHRH analogues goserelin and leuprorelin, although no direct comparison has yet been undertaken.

Current concepts in the pharmacotherapy of benign prostatic hyperplasia.

Benign prostatic hyperplasia is a major men's health issue, with approximately 80% of all men developing this condition within their lifetime. A variety of oral treatments is available, including alpha-adrenoceptor antagonists (alpha-blockers), 5alpha reductase inhibitors, aromatase inhibitors and phytotherapy. A large number of alpha-blockers can be administered, but no single agent has demonstrated a clear superiority over the other drugs. 5alpha Reductase inhibitors have demonstrated similar efficacy in larger volume prostates but most evidence suggests that there is no benefit in combining them with alpha-blockers. The use of phytotherapy is not entirely novel but requires further long-term evaluation before it can be endorsed for clinical use in benign prostatic hyperplasia.