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Background: Active surveillance (AS) is a management option for men diagnosed with low-risk prostate cancer. Opinions differ on whether it is safe to include young men (≤60 yr) or men with intermediate-risk disease., Objective: To assess whether reasons for discontinuation, treatment choice after AS, and adverse pathology at radical prostatectomy (RP; N1, or ≥GG3, or ≥pT3) differ for men ≤60 yr or those with European Association of Urology (EAU) intermediate-risk disease from those for men >60 yr or those with EAU low-risk disease., Design Setting and Participants: We analyzed data from 5411 men ≤60 yr and 14 959 men >60 yr, 14 064 men with low-risk cancer, and 2441 men with intermediate-risk cancer, originating from the GAP3 database (21 169 patients/27 cohorts worldwide)., Outcome Measurements and Statistical Analysis: Cumulative incidence curves were used to estimate the rates of AS discontinuation and treatment choice., Results and Limitations: The probability of discontinuation of AS due to disease progression at 5 yr was similar for men aged ≤60 yr (22%) and those >60 yr (25%), as well as those of any age with low-risk disease (24%) versus those with intermediate-risk disease (24%). Men with intermediate-risk disease are more prone to discontinue AS without evidence of progression than men with low-risk disease (at 1/5 yr: 5.9%/14.2% vs 2.0%/8.8%). Adverse pathology at RP was observed in 32% of men ≤60 yr compared with 36% of men >60 yr ( p  = 0.029), and in 34% with low-risk disease compared with 40% with intermediate-risk disease ( p  = 0.048)., Conclusions: Our descriptive analysis of AS practices worldwide showed that the risk of progression during AS is similar across the age and risk groups studied. The proportion of adverse pathology was higher among men >60 yr than among men ≤60 yr. These results suggest that men ≤60 yr and those with EAU intermediate-risk disease should not be excluded from opting for AS as initial management., Patient Summary: Data from 27 international centers reflecting daily clinical practice suggest that younger men or men with intermediate-risk prostate cancer do not hold greater risk for disease progression during active surveillance., (© 2022 The Author(s).)

Background: Studies of active surveillance (AS) for prostate cancer (PCa) have focussed predominantly on Caucasian populations. Little is known about the experience of Asian men, while suitability for men of African descent has been questioned., Objective: To compare baseline characteristics, follow-up, and outcomes for men on AS for PCa, according to ethnicity., Design Setting and Participants: The study cohort included 13 centres from the GAP3 consortium that record ethnicity (categorised broadly as Caucasian/white, African/Afro-Caribbean/black, Asian, mixed/other, and unknown). Men with biopsy grade group >2, prostate-specific antigen (PSA) >20 ng/ml, T stage ≥cT3, or age >80 yr were excluded., Outcome Measurements and Statistical Analysis: Clinical characteristics, follow-up schedules, outcome status, and reasons for discontinuation were compared across ethnic groups. Risk of upgrading, potential disease progression (grade group ≥3 or T stage ≥3), suspicious indications (any upgrading, number of positive cores >3, T stage ≥cT3, PSA >20 ng/ml, or PSA density >0.2 ng/ml/cc 2 ), and conversion to treatment were assessed using mixed-effect regression models., Results and Limitations: The eligible cohort ( n = 9158) comprised 83% Caucasian men, 6% men of African descent, 5% Asian men, 2% men of mixed/other ethnicity, and 4% men of unknown ethnicity. Risks of suspicious indicators (hazard ratio = 1.27; 95% confidence interval [CI] 1.12-1.45), upgrading (odds ratio [OR] = 1.40; 95% CI 1.14-1.71), and potential progression (OR = 1.46; 95% CI 1.06-2.01) were higher among African/black than among Caucasian/white men. Risk of transitioning to treatment did not differ by ethnicity. More Asian than Caucasian men converted without progression (42% vs 26%, p < 0.001). Heterogeneity in surveillance protocols and racial makeup limit interpretation., Conclusions: This multinational study found differences in the risk of disease progression and transitioning to treatment without signs of progression between ethnic groups. Further research is required to determine whether differences are due to biology, sociocultural factors, and/or clinical practice., Patient Summary: This international study compared prostate cancer active surveillance outcomes by ethnicity. Risks of upgrading and disease progression were higher among African than among Caucasian men. Transitioning to treatment without progression was highest among Asian men. Understanding of these differences requires further investigation., (© 2021 The Author(s).)

Background: The routine clinical use of serum prostatic specific antigen (PSA) testing has allowed earlier detection of low-grade prostate cancer (PCa) with more favourable characteristics, leading to increased acceptance of management by active surveillance (AS). AS aims to avoid over treatment in men with low and intermediate-risk PCa and multiple governing bodies have described several AS protocols. This study provides a descriptive profile of the Guy's and St Thomas NHS Foundation Trust (GSTT) AS cohort as a platform for future research in AS pathways in PCa., Methods: Demographic and baseline characteristics were retrospectively collected in a database for patients at the GSTT AS clinic with prospective collection of follow-up data from 2012. Seven hundred eighty-eight men being monitored at GSTT with histologically confirmed intermediate-risk PCa, at least 1 follow-up appointment and diagnostic characteristics consistent with AS criteria were included in the profile. Descriptive statistics, Kaplan-Meier survival curves and multivariable Cox proportion hazards regression models were used to characterize the cohort., Discussion: A relatively large proportion of the cohort includes men of African/Afro-Caribbean descent (22%). More frequent use of magnetic resonance imaging and trans-perineal biopsies at diagnosis was observed among patients diagnosed after 2012. Those who underwent trans-rectal ultrasound diagnostic biopsy received their first surveillance biopsy 20 months earlier than those who underwent trans-perineal diagnostic biopsy. At 3 years, 76.1% men remained treatment free. Predictors of treatment progression included Gleason score 3 + 4 (Hazard ratio (HR): 2.41, 95% Confidence interval (CI): 1.79-3.26) and more than 2 positive cores taken at biopsy (HR: 2.65, CI: 1.94-3.62). A decreased risk of progressing to treatment was seen among men diagnosed after 2012 (HR: 0.72, CI: 0.53-0.98)., Conclusion: An organised biopsy surveillance approach, via two different AS pathways according to the patient's diagnostic method, can be seen within the GSTT cohort. Risk of patients progressing to treatment has decreased in the period since 2012 compared with the prior period with more than half of the cohort remaining treatment free at 5 years, highlighting that the fundamental aims of AS at GSTT are being met. Thus, this cohort is a good resource to investigate the AS treatment pathway.

Interleukin-15 (IL-15) is a cytokine that has been shown to expand CD8 T cell and natural killer (NK) cell populations, and therefore has potential for potentiating adoptive immune cell therapy for cancer. Previously, IL-15 has been shown to induce proliferation of CD8 memory T cells through activation of telomerase. Here, we investigated whether telomerase is also activated during the IL-15 mediated proliferation of NK and NKT-like (CD56+CD3+) cells. We also examined the extent that each of the three signaling pathways known to be stimulated by IL-2/IL-15 (JAK-STAT, PI3K-AKT Ras-RAF/MAPK) were activated and involved in the telomerase expression in the three cell types NK, NKT, or CD8 T cells. To assess cell proliferation and doubling, peripheral blood mononuclear cells (PBMCs) or isolated NK, NKT-like or CD8 T cells were incubated with varying concentrations of IL-15 or IL-2 for 7 days. CD8 T, NK, and NKT cell expansion was determined by fluorophore-conjugated antibody staining and flow cytometry. Cell doubling was investigated using carboxyfluorescein-succinimidyl-ester (CFSE). Telomerase expression was investigated by staining cells with anti-telomerase reverse transcriptase (anti-TERT). Telomerase activity in CD56+ and CD8 T cells was also measured via Telomerase Repeat Amplification Protocol (TRAP). Analysis of cellular expansion, proliferation and TERT expression concluded that IL-15 increased cellular growth of NK, NKT, and CD8 T cells more effectively than IL-2 using low or high doses. IL-15, increased TERT expression in NK and NKT cells by up to 2.5 fold, the same increase seen in CD8 T cells. IL-2 had effects on TERT expression only at high doses (100-1000 ng/ml). Proteome profiling identified that IL-15 activated selected signaling proteins in the three pathways (JAK-STAT, PI3K-AKT, Ras-MAPK) known to mediate IL-2/IL-15 signaling, more strongly than IL-2. Evaluation by signaling pathway inhibitors revealed that JAK/STAT and PI3K/AKT pathways are important in IL-15's ability to upregulate TERT expression in NK and NKT cells, whereas all three pathways were involved in CD8 T cell TERT expression. In conclusion, this study shows that IL-15 potently stimulates TERT upregulation in NK and NKT cells in addition to CD8 T cells and is therefore a valuable tool for adoptive cell therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Watkinson, Nayar, Rani, Sakellariou, Elhage, Papaevangelou, Dasgupta and Galustian.)

Nerve-sparing robot-assisted radical prostatectomy has decreased the post-surgical complications of prostate surgery, but has not eliminated it. The ability to view the microstructure will enable better surgical decisions and lead to better post-surgical outcomes. An ideal imaging modality should provide rapid image acquisition, be low cost, and be specific to the tissue being examined. This article aims to review the current literature to compare three main techniques: multiphoton microscopy (MPM), optical coherence tomography, and confocal microscopy, to see which of these techniques may be best applied in surgical procedures in the future. Embase and Medline were used as the primary databases. Combinations of various key words were used while researching the literature. These included: "Radical prostatectomy," "nerve-sparing," "nerve mapping," "multiphoton microscopy," "Confocal microscopy," and "Optical Coherence Tomography." Thereafter, the relevant results were selected and used in the review. Although optical coherence tomography is a low cost and compact modality, it lacks cellular resolution, while confocal microscopy offers great cellular resolution but lacks depth. MPM, on the other hand, provides sufficient depth and produces high-resolution images. The limitation of MPM is its lack of portability, however the advent of dual-modality MPM may be a way forward.

A 56-year-old man was admitted to hospital with shortness of breath and subsequently sustained a cardiac arrest. In the recovery period, he developed acute urinary retention and haematuria. Imaging suggested an enlarged prostate and he was started on clean intermittent catheterisation. Following further imaging and a transurethral biopsy, he was found to have a bladder leiomyoma. This was treated with laparotomy, cystotomy and enucleation of the tumour. At his 6-week follow-up appointment, he had a satisfactory cystogram and a successful void without catheter., (2016 BMJ Publishing Group Ltd.)

Objectives: Discussion of the evolution of image guided surgery (IGS) and its fundamental components and current evidence for effectiveness of IGS in clinical urology., Methods: Literature search for image-guided robotic urology., Results: Current literature in image-guided robotic urology with its use in robot assisted radical prostatectomy and robot assisted partial nephrectomy are shown., Conclusions: Image guided surgery can be a useful aid to improve visualisation of anatomy and subsurface structures during minimally invasive surgery. Soft-tissue deformation makes it difficult to implement IGS in urology but current studies have shown an attempt to address this issue. The feasibility of IGS requires randomised control trials assessing in particular its accuracy and affect on clinical outcome.

Introduction: This study aims to establish face, content and construct validation of the SEP Robot (SimSurgery, Oslo, Norway) in order to determine its value as a training tool., Subjects and Methods: The tasks used in the validation of this simulator were arrow manipulation and performing a surgeon's knot. Thirty participants (18 novices, 12 experts) completed the procedures., Results: The simulator was able to differentiate between experts and novices in several respects. The novice group required more time to complete the tasks than the expert group, especially suturing. During the surgeon's knot exercise, experts significantly outperformed novices in maximum tightening stretch, instruments dropped, maximum winding stretch and tool collisions in addition to total task time. A trend was found towards the use of less force by the more experienced participants., Conclusions: The SEP robotic simulator has demonstrated face, content and construct validity as a virtual reality simulator for robotic surgery. With steady increase in adoption of robotic surgery world-wide, this simulator may prove to be a valuable adjunct to clinical mentorship.

Introduction: Hypertension is a common medical problem mainly treated by effective antihypertensive drugs. Persistent hypertension can be difficult to manage and have detrimental effect on vital organs. Nephrectomy of poorly functioning kidneys may be indicated in a minority of such cases., Patients and Methods: We performed laparoscopic nephrectomy on 12 patients with refractory hypertension., Results: Eight had complete response, three had partial response and one had no response., Conclusions: Laparoscopic nephrectomy has a role in carefully selected adult patients with refractory hypertension due to non-functioning kidney. Patients need to understand the surgical risks as well as the small risk of failure to treat hypertension.