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.

Negative Prebiopsy Magnetic Resonance Imaging and Risk of Significant Prostate Cancer: Baseline and Long-Term Followup Results.

PURPOSE: Prostate biopsy should be discussed with the patient in cases of negative magnetic resonance imaging and low clinical suspicion of prostate cancer.Our primary objective was to describe the risk of clinically significant prostate cancer in a negative magnetic resonance imaging biopsy naïve population at baseline and during long-term followup. The secondary objective was to evaluate clinical factors and prostate specific antigen as predictors of clinically significant prostate cancer at baseline. MATERIALS AND METHODS: All 503 consecutive patients who were biopsy naïve referred from 2007 to 2017 for biopsy with negative magnetic resonance imaging (PI-RADS™ 1-2) who had systematic 12-core biopsies at baseline were included. Clinical factors were digital rectal examination, prostate cancer family history and prostate specific antigen. In case of suspicious digital rectal examination or prostate specific antigen kinetics during followup, magnetic resonance imaging and biopsy were performed. Clinically significant prostate cancer was defined as either Gleason Grade 1 with cancer core length greater than 5 mm or 3 or more positive systematic 12-core biopsies in addition to Gleason Grade 2 or greater (clinically significant prostate cancer-1) or any Gleason Grade 2 or greater (clinically significant prostate cancer-2). Nonclinically significant prostate cancer was defined as either Gleason Grade 1 with cancer core length 5 mm or less and fewer than 3 positive systematic 12-core biopsies (nonclinically significant prostate cancer-1) or any Gleason Grade 1 (nonclinically significant prostate cancer-2). Definition of high risk clinically significant prostate cancer was Gleason Grade 3 or greater. Univariate and multivariate models were fitted to identify predictors of clinically significant prostate cancer risk. RESULTS: At baseline, biopsy showed clinically significant prostate cancer-1 in 9% (45), clinically significant prostate cancer-2 in 6% (29) and nonclinically significant prostate cancer in 22% (111). At median followup of 4 years (IQR 1.6-7.1), 31% (95% CI 27-36) of 415 untreated patients had a second magnetic resonance imaging and 24% (95% CI 20-28) a second biopsy that showed clinically significant prostate cancer-1 in 5% (21/415, 95% CI 3-7), clinically significant prostate cancer-2 in 2% (7/415, 95% CI 1-3) and nonclinically significant prostate cancer in 8%. Overall incidence was 13% (66/503, 95% CI 7-21) for clinically significant prostate cancer-1, 7% (36/503, 95% CI 5-9%) for clinically significant prostate cancer-2 and 2% (12/503, 95% CI 1.1-3.7) for high risk prostate cancer. Predictors of clinically significant prostate cancer risk were prostate specific antigen density 0.15 ng/ml/ml or greater (OR 2.43, 1.19-4.21), clinical stage T2a or greater (OR 3.32, 1.69-6.53) and prostate cancer family history (OR 2.38, 1.10-6.16). Performing biopsy in patients with negative magnetic resonance imaging and prostate specific antigen density 0.15 ng/ml/ml or greater or abnormal digital rectal examination or prostate cancer family history would have decreased from 9% to 2.4% the risk of missing clinically significant prostate cancer-1 at baseline while avoiding biopsy in 56% of cases. CONCLUSIONS: The risk of clinically significant prostate cancer in a negative magnetic resonance imaging biopsy naïve population was 6% to 9% at baseline and 7% to 13% at long-term followup depending on clinically significant prostate cancer definitions.

Conspicuity of prostate cancer on multiparametric magnetic resonance imaging: A cross-disciplinary translational hypothesis.

Pre-biopsy multiparametric magnetic resonance imaging (mpMRI) has transformed the risk stratification and diagnostic approach for suspected prostate cancer. The majority of clinically significant prostate cancers are visible on pre-biopsy mpMRI, however, there are a subset of significant tumors that are not detected by mpMRI. The radiobiological mechanisms underpinning mpMRI-visibility and invisibility of these cancers remain uncertain. Emerging evidence suggests that mpMRI-visible tumors are enriched with molecular features associated with increased disease aggressivity and poor clinical prognosis, which is supported by short-term endpoints, such as biochemical recurrence following surgery. Furthermore, at the histopathological level, mpMRI-visible tumors appear to exhibit increased architectural and vascular density compared to mpMRI-invisible disease. It seems probable that the genomic, pathological, radiological, and clinical features of mpMRI-visible and mpMRI-invisible prostate cancers are interrelated. Here, we propose a novel cross-disciplinary theory that links genomic and molecular evidence with cellular and histopathological appearances, elucidating both the mpMRI visibility and clinical status of significant prostate cancer.

Diagnostic pitfalls of urogenital tuberculosis.

OBJECTIVES: To describe characteristics, details of diagnosis and outcomes of urogenital tuberculosis (UGTB) in a low-prevalence country. METHODS: We conducted a retrospective observational study of 37 consecutive patients diagnosed with UGTB between 1st January 2014 and 31st October 2019 in an East London hospital. RESULTS: 68% (25/37) of patients were male and the median age was 42 years (IQR 34-55). 89% (33/37) of patients were born outside the United Kingdom with 65% (24/37) born in the South Asian region. Renal (32.4%), epididymal (24.3%) and endometrial TB (21.6%) were the most prevalent forms of UGTB. Only 13.5% of UGTB patients had concurrent pulmonary TB. The median length of time from symptom onset to treatment was 163 days, while endometrial TB had an average delay to diagnosis of 564 days. Approximately half of patients with UGTB were culture positive (51.4%). However, 70% of early morning urines (EMUs) sent in urinary TB were culture positive. 11 patients (30.6%) underwent two or more invasive procedures, such as biopsy to obtain specimen samples. The mean treatment length for all UGTB cases was 7.3 months (SD 3.1). Notably, 25% of patients with endometrial TB required surgery despite antituberculous treatment. CONCLUSIONS: UGTB is challenging to diagnose as early disease is often asymptomatic. Clinicians faced with non-specific symptoms, or features suggestive of urogenital malignancy amongst patients from TB-endemic areas, should maintain a high suspicion of UGTB.

Developments in MRI-targeted prostate biopsy.

PURPOSE OF REVIEW: MRI-targeted prostate biopsy may be an attractive alternative to systematic biopsy for diagnosing clinically significant prostate cancer. In this narrative review, we discuss the new developments that have occurred in the advancement of MRI-targeted prostate biopsy, over the past 24 months. RECENT FINDINGS: MRI-targeted biopsy offers enhanced diagnostic accuracy, when compared with the current standard of care of systematic transrectal ultrasound-guided (TRUS) biopsy, by decreasing the overall number of biopsies needed, maintaining or improving significant prostate cancer detection, and reducing the detection of clinically insignificant prostate cancer. The necessity of combining systematic prostate biopsy with MRI-targeted biopsy is still debated. The use of MRI--ultrasound fusion systems for lesion-targeting is promising for optimizing significant cancer detection, but recent evidence suggests that additional cognitive biopsy cores are still useful in detecting additional cancers. SUMMARY: MRI-targeted biopsy in selected men with positive MRI offers a number of benefits over systematic biopsy in all men, and as such, may emerge as the new standard of care for the diagnosis of clinically significant prostate cancer.

Surface tension of a Yukawa fluid according to mean-field theory.

Yukawa fluids consist of particles that interact through a repulsive or attractive Yukawa potential. A surface tension arises at the walls of the container that encloses the fluid or at the interface between two coexisting phases. We calculate that surface tension on the level of mean-field theory, thereby either ignoring the particle size (ideal Yukawa fluid) or accounting for a non-vanishing particle size through a nonideal contribution to the free energy, exemplified either on the level of a lattice gas (lattice Yukawa fluid) or based on the Carnahan-Starling equation of state (Carnahan-Starling Yukawa fluid). Our mean-field results, which do not rely on assuming small gradients of the particle concentrations, become exact in the limit of large temperature and large screening length. They are calculated numerically in the general case and analytically in the two limits of small particle concentration and close to the critical point for a phase-separating system. For a sufficiently small particle concentration, our predicted surface tension is accurate whereas for a phase boundary, we expect good agreement with exact calculations in the limit of a large screening length and if the mean-field model employs the Carnahan-Starling equation of state.

A rationally designed mutant of plasma platelet-activating factor acetylhydrolase hydrolyzes the organophosphorus nerve agent soman.

Organophosphorus compounds (OPs) such as sarin and soman are some of the most toxic chemicals synthesized by man. They exert toxic effects by inactivating acetylcholinesterase (AChE) and bind secondary target protein. Organophosphorus compounds are hemi-substrates for enzymes of the serine hydrolase superfamily. Enzymes can be engineered by amino acid substitution into OP-hydrolyzing variants (bioscavengers) and used as therapeutics. Some enzymes associated with lipoproteins, such as human plasma platelet-activating factor acetylhydrolase (pPAF-AH), are also inhibited by OPs; these proteins have largely been ignored for engineering purposes because of complex interfacial kinetics and a lack of structural data. We have expressed active human pPAF-AH in bacteria and previously solved the crystal structure of this enzyme with OP adducts. Using these structures as a guide, we created histidine mutations near the active site of pPAF-AH (F322H, W298H, L153H) in an attempt to generate novel OP-hydrolase activity. Wild-type pPAF-AH, L153H, and F322H have essentially no hydrolytic activity against the nerve agents tested. In contrast, the W298H mutant displayed novel somanase activity with a kcat of 5min(-1) and a KM of 590µM at pH7.5. There was no selective preference for hydrolysis of any of the four soman stereoisomers.

Robotic pyeloplasty: Technological global panacea or geo-surgical nightmare?

To the Editor, Pelvi-ureteric junction obstruction (PUJO) is a well-recognised clinical entity characterised by functionally significant impairment of drainage of urine at the level of the pelvi-ureteric junction due to extrinsic or intrinsic obstruction and is encountered both by adult and paediatric urologists alike. Management of PUJO has been surgical historically, and the gold standard has been an open Anderson-Hynes dismembered pyeloplasty [...].

Comparison of outcomes of open, laparoscopic and robot-assisted laparoscopic pyeloplasty in children with ureteropelvic junction obstruction: protocol for a systematic review and meta-analysis.

INTRODUCTION: The treatment of children with pelviureteric junction obstruction (PUJO) has naturally progressed from open, to minimally invasive approaches, including laparoscopic pyeloplasty and robot-assisted laparoscopic pyeloplasty (RALP). The RALP is now considered to be the gold standard for paediatric patients with PUJO, except for smaller infants due to size limitations. Our systematic review aims to synthesise all the available evidence regarding key postoperative outcomes for the three surgical approaches to pyeloplasties in children. Our outcomes of interest include, but are not limited to, the reoperation rate, length of hospital stay and postoperative complications as classified by the Clavien-Dindo grading system. A comprehensive assessment of all three methods in paediatric patients has yet to be conducted in the literature to date. METHODS AND ANALYSIS: A systematic search of the MEDLINE, PubMed, EMBASE and Cochrane databases will be conducted. Screening, data extraction, statistical analysis and reporting will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included papers will be full-text manuscripts written between 1947 and March 2024, comparing the outcomes and complications of open, laparoscopic and RALP. Quality and study bias will be assessed using the Newcastle-Ottawa score and, if relevant, the Cochrane risk of bias tool for randomised trials. This present protocol is written in accordance with the PRISMA Protocol 2015 checklist, ensuring that the highest methodological standards are adhered to. ETHICS AND DISSEMINATION: No ethical approval shall be required, as this is a review of already published literature. Findings will be disseminated through publications in peer-reviewed journals and presentations at international and national conferences. PROSPERO REGISTRATION NUMBER: CRD42023456779.

Comparison of Outcomes of Active Surveillance in Intermediate-Risk Versus Low-Risk Localised Prostate Cancer Patients: A Systematic Review and Meta-Analysis.

Currently, there is no clear consensus regarding the role of active surveillance (AS) in the management of intermediate-risk prostate cancer (IRPC) patients. We aim to analyse data from the available literature on the outcomes of AS in the management of IRPC patients and compare them with low-risk prostate cancer (LRPC) patients. A comprehensive literature search was performed, and relevant data were extracted. Our primary outcome was treatment-free survival, and secondary outcomes were metastasis-free survival, cancer-specific survival, and overall survival. The DerSimonian-Laird random-effects method was used for the meta-analysis. Out of 712 studies identified following an initial search, 25 studies were included in the systematic review. We found that both IRPC and LRPC patients had nearly similar 5, 10, and 15 year treatment-free survival rate, 5 and 10 year metastasis-free survival rate, and 5 year overall survival rate. However, cancer-specific survival rates at 5, 10, and 15 years were significantly lower in IRPC compared to LRPC group. Furthermore, IRPC patients had significantly inferior long-term overall survival rate (10 and 15 year) and metastasis-free survival rate (15 year) compared to LRPC patients. Both the clinicians and the patients can consider this information during the informed decision-making process before choosing AS.

Use of artificial intelligence in the detection of primary prostate cancer in multiparametric MRI with its clinical outcomes: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Multiparametric MRI (mpMRI) has transformed the prostate cancer diagnostic pathway, allowing for improved risk stratification and more targeted subsequent management. However, concerns exist over the interobserver variability of images and the applicability of this model long term, especially considering the current shortage of radiologists and the growing ageing population. Artificial intelligence (AI) is being integrated into clinical practice to support diagnostic and therapeutic imaging analysis to overcome these concerns. The following report details a protocol for a systematic review and meta-analysis investigating the accuracy of AI in predicting primary prostate cancer on mpMRI. METHODS AND ANALYSIS: A systematic search will be performed using PubMed, MEDLINE, Embase and Cochrane databases. All relevant articles published between January 2016 and February 2023 will be eligible for inclusion. To be included, articles must use AI to study MRI prostate images to detect prostate cancer. All included articles will be in full-text, reporting original data and written in English. The protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 checklist. The QUADAS-2 score will assess the quality and risk of bias across selected studies. ETHICS AND DISSEMINATION: Ethical approval will not be required for this systematic review. Findings will be disseminated through peer-reviewed publications and presentations at both national and international conferences. PROSPERO REGISTRATION NUMBER: CRD42021293745.

Diagnostic potential of radiological apical tumor involvement.

We commend Veerman et al. for investigating the diagnostic performance of radiological apical tumor involvement (radATI) in preoperative prostate magnetic resonance imaging (MRI) and its impact on clinical outcomes in patients with localized prostate cancer. This retrospective study evaluated the diagnostic accuracy of MRI to detect pathological ATI (pathATI) in robot-assisted radical prostatectomy specimens. They found patients with radATI more likely to develop biochemical recurrence (BCR), p = 0.003, and have apical positive surgical margins (APSM), p = 0.004. We believe that the author's acknowledgement of the relationship between tumor location and cancer risk is an important step in the classification of prostate cancer. An important question that is under addressed is, what is it about apical tumors that carry additional risk? Higher rates of PSM due to incomplete surgical excision may contribute to increased recurrence risk in the apex. If this is the case, surgical management must be tailored by a tumor location-based risk assessment. The literature suggests that a single APSM may be clinically insignificant for long-term outcomes. Conversely, the authors also recommend radATI be treated with reduced apical nerve sparing to avoid APSM. We believe that this approach may lead to overtreatment in the presence of an otherwise good prognosis. We believe the extent of APSMs upon diagnosis would be an interesting topic for further investigation. The authors may also wish to perform multivariable analysis for the effect of radATI on BCR. We believe that MRI may play a critical role in enhancing diagnosis and prognostication of prostate cancer.

Prostate cancer and the human papilloma virus: causative association, role of vaccines, and the impact of the COVID-19 pandemic.

Prostate cancer affects a significant proportion of men worldwide. Evidence from genetic and clinical studies suggests that there may be a causal association between prostate cancer and the human papilloma virus (HPV). As HPV is a vaccine-preventable pathogen, the possibility of a role in prostate cancer causation may reinforce the importance of effective HPV vaccination campaigns. This is of particular relevance in light of the COVID-19 pandemic, which may have considerable effects on HPV vaccine uptake and distribution.