exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids.

To develop a map of cell-cell communication mediated by extracellular RNA (exRNA), the NIH Extracellular RNA Communication Consortium created the exRNA Atlas resource (https://exrna-atlas.org). The Atlas version 4P1 hosts 5,309 exRNA-seq and exRNA qPCR profiles from 19 studies and a suite of analysis and visualization tools. To analyze variation between profiles, we apply computational deconvolution. The analysis leads to a model with six exRNA cargo types (CT1, CT2, CT3A, CT3B, CT3C, CT4), each detectable in multiple biofluids (serum, plasma, CSF, saliva, urine). Five of the cargo types associate with known vesicular and non-vesicular (lipoprotein and ribonucleoprotein) exRNA carriers. To validate utility of this model, we re-analyze an exercise response study by deconvolution to identify physiologically relevant response pathways that were not detected previously. To enable wide application of this model, as part of the exRNA Atlas resource, we provide tools for deconvolution and analysis of user-provided case-control studies.

Racial disparity in prostate cancer: an outlook in genetic and molecular landscape.

Prostate cancer (PCa) incidence, morbidity, and mortality rates are significantly impacted by racial disparities. Despite innovative therapeutic approaches and advancements in prevention, men of African American (AA) ancestry are at a higher risk of developing PCa and have a more aggressive and metastatic form of the disease at the time of initial PCa diagnosis than other races. Research on PCa has underlined the biological and molecular basis of racial disparity and emphasized the genetic aspect as the fundamental component of racial inequality. Furthermore, the lower enrollment rate, limited access to national-level cancer facilities, and deferred treatment of AA men and other minorities are hurdles in improving the outcomes of PCa patients. This review provides the most up-to-date information on various biological and molecular contributing factors, such as the single nucleotide polymorphisms (SNPs), mutational spectrum, altered chromosomal loci, differential gene expression, transcriptome analysis, epigenetic factors, tumor microenvironment (TME), and immune modulation of PCa racial disparities. This review also highlights future research avenues to explore the underlying biological factors contributing to PCa disparities, particularly in men of African ancestry.

Link between circadian rhythm and benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS).

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common urologic disease in aging males, affecting 50% of men over 50 and up to 80% of men over 80 years old. Its negative impact on health-related quality of life implores further investigation into its risk factors and strategies for effective management. Although the exact molecular mechanisms underlying pathophysiological onset of BPH are poorly defined, the current hypothesized contributors to BPH and lower urinary tract symptoms (LUTS) include aging, inflammation, metabolic syndrome, and hormonal changes. These processes are indirectly influenced by circadian rhythm disruption. In this article, we review the recent evidence on the potential association of light changes/circadian rhythm disruption and the onset of BPH and impact on treatment. METHODS: A narrative literature review was conducted using PubMed and Google Scholar to identify supporting evidence. The articles referenced ranged from 1975 to 2023. RESULTS: A clear relationship between BPH/LUTS and circadian rhythm disruption is yet to be established. However, common mediators influence both diseases, including proinflammatory states, metabolic syndrome, and hormonal regulation that can be asserted to circadian disruption. Some studies have identified a possible relationship between general LUTS and sleep disturbance, but little research has been done on the medical management of these diseases and how circadian rhythm disruption further affects treatment outcomes. CONCLUSIONS: There is evidence to implicate a relationship between BPH/LUTS and circadian rhythm disruptions. However, there is scarce literature on potential specific link in medical management of the disease and treatment outcomes with circadian rhythm disruption. Further study is warranted to provide BPH patients with insights into circadian rhythm directed appropriate interventions.

Saline-assisted fascial exposure (SAFE) technique to improve nerve-sparing in robot-assisted laparoscopic radical prostatectomy.

OBJECTIVE: To provide a summary of our initial experience and assess the impact of the Saline-Assisted Fascial Exposure (SAFE) technique on erectile function (EF), urinary continence, and oncological outcomes after Robot-Assisted Laparoscopic Radical Prostatectomy (RALP). PATIENTS AND METHODS: From January 2021 to July 2022, we included patients with a baseline Sexual Health Inventory for Men (SHIM) score of ≥17 and a high probability of extracapsular extension (ECE), ranging from 21% to 73%, as per the Martini et al. nomogram. A propensity score matching was carried out at a ratio of 1:2 between patients who underwent RALP + SAFE (33) and RALP alone (66). The descriptive statistical analysis is presented. The SAFE technique was performed using two approaches, transrectal guided by micro-ultrasound or transperitoneal. Its principle entails a low-pressure injection of saline solution in the periprostatic fascia to achieve an atraumatic dissection of the neural hammock. Potency was defined as a SHIM score of ≥17 and continence as no pads per day. RESULTS: At follow-up intervals of 6, 13, 26, and 52 weeks, the SHIM score differed significantly between the two groups, favouring the RALP + SAFE (P = 0.01, P < 0.001, P < 0.001, and P = 0.01, respectively). These results remained significant when the mean SHIM score was assessed. As shown by the cumulative incidence curve, EF rates were higher in the RALP + SAFE compared to the RALP alone group (log-rank P < 0.001). The baseline SHIM and use of the SAFE technique were independent predictors of EF recovery. CONCLUSIONS: The use of the SAFE technique led to better SHIM scores at 6, 13, 26, and 52 weeks after RALP in patients at high risk of ECE who underwent a partial NS procedure.

Prostate cancer in transgender women: considerations for screening, diagnosis and management.

Transgender individuals represent 0.55% of the US population, equivalent to 1.4 million transgender adults. In transgender women, feminisation can include a number of medical and surgical interventions. The main goal is to deprive the phenotypically masculine body of androgens and simultaneously provide oestrogen therapy for feminisation. In gender-confirming surgery (GCS) for transgender females, the prostate is usually not removed. Due to limitations of existing cohort studies, the true incidence of prostate cancer in transgender females is unknown but is thought to be less than the incidence among cis-gender males. It is unclear how prostate cancer develops in androgen-deprived conditions in these patients. Six out of eleven case reports in the literature presented with metastatic disease. It is thought that androgen receptor-mediated mechanisms or tumour-promoting effects of oestrogen may be responsible. Due to the low incidence of prostate cancer identified in transgender women, there is little evidence to drive specific screening recommendations in this patient subpopulation. The treatment of early and locally advanced prostate cancer in these patients warrants an individualised thoughtful approach with input from patients' reconstructive surgeons. Both surgical and radiation treatment for prostate cancer in these patients can profoundly impact the patient's quality of life. In this review, we discuss the evidence surrounding screening and treatment of prostate cancer in transgender women and consider the current gaps in our knowledge in providing evidence-based guidance at the molecular, genomic and epidemiological level, for clinical decision-making in the management of these patients.

Association between Expression of Connective Tissue Genes and Prostate Cancer Growth and Progression.

To find an association between genomic features of connective tissue and pejorative clinical outcomes on radical prostatectomy specimens. We performed a retrospective analysis of patients who underwent radical prostatectomy and underwent a Decipher transcriptomic test for localized prostate cancer in our institution (n = 695). The expression results of selected connective tissue genes were analyzed after multiple t tests, revealing significant differences in the transcriptomic expression (over- or under-expression). We investigated the association between transcript results and clinical features such as extra-capsular extension (ECE), clinically significant cancer, lymph node (LN) invasion and early biochemical recurrence (eBCR), defined as earlier than 3 years after surgery). The Cancer Genome Atlas (TCGA) was used to evaluate the prognostic role of genes on progression-free survival (PFS) and overall survival (OS). Out of 528 patients, we found that 189 had ECE and 27 had LN invasion. The Decipher score was higher in patients with ECE, LN invasion, and eBCR. Our gene selection microarray analysis showed an overexpression in both ECE and LN invasion, and in clinically significant cancer for COL1A1, COL1A2, COL3A1, LUM, VCAN, FN1, AEBP1, ASPN, TIMP1, TIMP3, BGN, and underexpression in FMOD and FLNA. In the TCGA population, overexpression of these genes was correlated with worse PFS. Significant co-occurrence of these genes was observed. When presenting overexpression of our gene selection, the 5-year PFS rate was 53% vs. 68% (p = 0.0315). Transcriptomic overexpression of connective tissue genes correlated to worse clinical features, such as ECE, clinically significant cancer and BCR, identifying the potential prognostic value of the gene signature of the connective tissue in prostate cancer. TCGAp cohort analysis showed a worse PFS in case of overexpression of the connective tissue genes.

Why do African-American men face higher risks for lethal prostate cancer?

PURPOSE OF REVIEW: African-American men in the USA have a higher incidence of and mortality from prostate cancer (PCa), with a longstanding debate about the cause for these worse outcomes. This review examines differences in tumour biology and socioeconomics for African-American and Non-Hispanic White (NHW) men to answer the question 'why AA men face higher risks for lethal PCa' and draw a management consensus to redress the imbalance. RECENT FINDINGS: Recent evidence from over the past 2 years suggests the reasons why African-American men face a higher risk of lethal PCa are multifactorial, with contributions from differences in tumour biology as well as socioeconomic and healthcare access factors. Regarding tumour biology, genomic and transcriptome profiling suggests African-American men have upregulated expression of genes related to inflammatory pathways with downregulation of DNA repair genes. In contrast, NHW men have higher DNA repair pathways and metabolic pathways involving glycolysis and cell cycle activity. In addition, epidemiological evidence suggests equal healthcare access ensures equal PCa specific outcomes, implying African-American men's disease is not inherently more lethal. However, differences in tumour biology remain, which may explain specific differences in PCa incidence and the clinical findings of African-American men's increased response to immunotherapy and radiotherapy in recent trials. SUMMARY: Regardless of racial differences in disease outcomes and the factors causing them, African-American and NHW men seem to have diseases unique to their ancestry. This supports the exploration of personalized PCa treatment approaches, leveraging translational basic science research to uncover these differences and devise specific individualized methods therapeutic regimes to address them.

Gold nanoshell-localized photothermal ablation of prostate tumors in a clinical pilot device study.

Biocompatible gold nanoparticles designed to absorb light at wavelengths of high tissue transparency have been of particular interest for biomedical applications. The ability of such nanoparticles to convert absorbed near-infrared light to heat and induce highly localized hyperthermia has been shown to be highly effective for photothermal cancer therapy, resulting in cell death and tumor remission in a multitude of preclinical animal models. Here we report the initial results of a clinical trial in which laser-excited gold-silica nanoshells (GSNs) were used in combination with magnetic resonance-ultrasound fusion imaging to focally ablate low-intermediate-grade tumors within the prostate. The overall goal is to provide highly localized regional control of prostate cancer that also results in greatly reduced patient morbidity and improved functional outcomes. This pilot device study reports feasibility and safety data from 16 cases of patients diagnosed with low- or intermediate-risk localized prostate cancer. After GSN infusion and high-precision laser ablation, patients underwent multiparametric MRI of the prostate at 48 to 72 h, followed by postprocedure mpMRI/ultrasound targeted fusion biopsies at 3 and 12 mo, as well as a standard 12-core systematic biopsy at 12 mo. GSN-mediated focal laser ablation was successfully achieved in 94% (15/16) of patients, with no significant difference in International Prostate Symptom Score or Sexual Health Inventory for Men observed after treatment. This treatment protocol appears to be feasible and safe in men with low- or intermediate-risk localized prostate cancer without serious complications or deleterious changes in genitourinary function.

Exosomes as A Next-Generation Diagnostic and Therapeutic Tool in Prostate Cancer.

Extracellular vesicles (EVs) have brought great momentum to the non-invasive liquid biopsy procedure for the detection, characterization, and monitoring of cancer. Despite the common use of PSA (prostate-specific antigen) as a biomarker for prostate cancer, there is an unmet need for a more specific diagnostic tool to detect tumor progression and recurrence. Exosomes, which are EVs that are released from all cells, play a large role in physiology and pathology, including cancer. They are involved in intercellular communication, immune function, and they are present in every bodily fluid studied-making them an excellent window into how cells are operating. With liquid biopsy, EVs can be isolated and analyzed, enabling an insight into a potential therapeutic value, serving as a vehicle for drugs or nucleic acids that have anti-neoplastic effects. The current application of advanced technology also points to higher-sensitivity detection methods that are minimally invasive. In this review, we discuss the current understanding of the significance of exosomes in prostate cancer and the potential diagnostic value of these EVs in disease progression.

Diagnostic and methodological evaluation of studies on the urinary shedding of SARS-CoV-2, compared to stool and serum: A systematic review and meta-analysis.

Investigating the infectivity of body fluid can be useful for preventative measures in the community and ensuring safety in the operating rooms and on the laboratory practices. We performed a literature search of clinical trials, cohorts, and case series using PubMed/MEDLINE, Google Scholar, and Cochrane library, and downloadable database of CDC. We excluded case reports and searched all-language articles for review and repeated until the final drafting. The search protocol was registered in the PROSPERO database. Thirty studies with urinary sampling for viral shedding were included. A total number of 1,271 patients were enrolled initially, among which 569 patients had undergone urinary testing. Nine studies observed urinary viral shedding in urine from 41 patients. The total incidence of urinary SARS-CoV-2 shedding was 8%, compared to 21.3% and 39.5 % for blood and stool, respectively. The summarized risk ratio (RR) estimates for urine positive rates compared to the pharyngeal rate was 0.08. The pertaining RR urine compared to blood and stool positive rates were 0.20 and 0.33, respectively. Our review concludes that not only the SARS-CoV-2 can be excreted in the urine in eight percent of patients but also its incidence may have associations with the severity of the systemic disease, ICU admission, and fatality rates. Moreover, the findings in our review suggest that a larger population size may reveal more positive urinary cases possibly by minimizing biases.

Radiomics Features Measured with Multiparametric Magnetic Resonance Imaging Predict Prostate Cancer Aggressiveness.

PURPOSE: We sought to 1) assess the association of radiomics features based on multiparametric magnetic resonance imaging with histopathological Gleason score, gene signatures and gene expression levels in prostate cancer and 2) build machine learning models based on radiomics features to predict adverse histopathological scores and the Decipher® genomics metastasis risk score. MATERIALS AND METHODS: We retrospectively analyzed the records of 64 patients with prostate cancer with a mean age of 64 years (range 41 to 76) who underwent magnetic resonance imaging between January 2016 and January 2017 before radical prostatectomy. A total of 226 magnetic resonance imaging radiomics features, including histogram and texture features in addition to lesion size and the PI-RADS™ (Prostate Imaging Reporting and Data System) score, were extracted from T2-weighted, apparent diffusion coefficient and diffusion kurtosis imaging maps. Radiomics features were correlated with the pathological Gleason score, 40 gene expression signatures, including Decipher, and 698 prostate cancer related gene expression levels. Cross-validated, lasso regularized, logistic regression machine learning models based on radiomics features were built and evaluated for the prediction of Gleason score 8 or greater and Decipher score 0.6 or greater. RESULTS: A total of 14 radiomics features significantly correlated with the Gleason score (highest correlation r = 0.39, p = 0.001). A total of 31 texture and histogram features significantly correlated with 19 gene signatures, particularly with the PORTOS (Post-Operative Radiation Therapy Outcomes Score) signature (strongest correlation r = -0.481, p = 0.002). A total of 40 diffusion-weighted imaging features correlated significantly with 132 gene expression levels. Machine learning prediction models showed fair performance to predict a Gleason score of 8 or greater (AUC 0.72) and excellent performance to predict a Decipher score of 0.6 or greater (AUC 0.84). CONCLUSIONS: Magnetic resonance imaging radiomics features are promising markers of prostate cancer aggressiveness on the histopathological and genomics levels.

An updated approach to incremental nerve sparing for robot-assisted radical prostatectomy.

OBJECTIVES: To update the algorithm for performing incremental nerve sparing (NS) using our multiparametric magnetic resonance imaging (mpMRI)-based nomogram. PATIENTS AND METHODS: We applied the coefficients of the nomogram to the observations extracted from our population of patients who underwent robot-assisted radical prostatectomy between February 2014 and October 2015 and who received preoperative mpMRI. The information considered were PSA level, highest side-specific biopsy Gleason grade group, highest ipsilateral percentage core involvement with the highest Gleason grade group, and extracapsular extension (ECE) on mpMRI. The nomogram-derived probability [P (%)], after internal validation, was used as the independent variable on a classification tree to identify the most significant thresholds for ECE prediction. Incremental NS was performed as follows: Grade 1 NS: intrafascial dissection between the peri-prostatic veins and the pseudocapsule of the prostate; Grade 2 NS: inter-fascial dissection along the peri-venous plane; Grade 3 NS: inter-fascial dissection through the outer compartment of the lateral prostatic fascia; Grade 4 NS: extrafascial dissection. RESULTS: Data from 561 patients were considered, and 829 prostatic lobes with biopsy-documented tumour were analysed. Overall, 142 lobes presented ECE that was focal in 27 (19%) cases. The classification tree identified four risk categories. In the low- [P (%) ≤10], intermediate- [P (%) 10-21], high [P (%) 21-73] and very-high-risk [P(%) >73] groups, the ECE rates were 3.3%, 16%, 61.6% and 90%, respectively. Amongst those, ECE was focal in 41.7%, 31.7%, 7.9% and 0%, respectively. CONCLUSION: We suggest that Grade 1 NS (intrafascial) should be performed in the low-risk group. The inter-fascial approach, namely grades 2 and 3 NS, should be performed in the intermediate- and high-risk categories, respectively. Grade 4 NS (extrafascial) should be performed in the very-high-risk group. The current algorithm yields a better accuracy than the previous one; however, prospective validation is warranted.

A transcriptomic signature of tertiary Gleason 5 predicts worse clinicopathological outcome.

OBJECTIVE: To investigate the genomic features of tertiary pattern 5 (TP5) on radical prostatectomy specimens in an effort to explain the poor clinical outcomes associated with this disease subtype. PATIENTS AND METHODS: Data from 159 men with Gleason Grade Group (GGG) 3 or 4 were considered. All patients had Decipher diagnostic testing with transcript profiles and single-channel array normalisation (SCAN)-normalised expression of coding genes. The relationship between Decipher and TP5 was investigated by linear and binary logistic regressions. A differential transcriptomic analysis between patients with and without TP5 was performed. The prognostic role of these genes on progression-free survival (PFS) and overall survival (OS) was evaluated using The Cancer Genome Atlas. RESULTS: In all, 52/159 (33%) patients had GGG 3-4 with TP5 disease. TP5 was associated with a higher Decipher score (ß 0.07, 95% confidence interval [CI] 0.02-0.13; P = 0.04) and higher likelihood of falling within the intermediate- or high-risk categories (odds ratio 3.34, 95% CI 1.34-8.35; P = 0.01). Analysis of microarray data revealed an 18-gene signature that was differentially expressed in patients with TP5; 13 genes were over- and five under-expressed in the TP5 cohort. The overexpression of cyclin dependent kinase inhibitor 2B (CDKN2B), polo-like kinase 1 (PLK1), or cell division cycle 20 (CDC20) was associated with worse PFS. The group harbouring overexpression of at least one gene had a 5-year PFS rate of 50% vs 74% in the group without overexpression (P < 0.001). CONCLUSIONS: Our studies have elucidated unique genomic features of TP5, whilst confirming previous clinical findings that patients harbouring TP5 tend to have worse prognosis. This is the first RNA-based study to investigate the molecular diversity of TP5 and the first correlating CDKN2B to poorer prognosis in patients with prostate cancer.

Image guidance in robot-assisted radical prostatectomy: how far do we stand?

PURPOSE OF REVIEW: Over the past decades, several efforts have been made for integrating multiparametric MRI (mpMRI) in the diagnostic pathways of prostate cancer. Despite this fact, the role of mpMRI in planning surgery has been explored in a relatively small number of studies. The aim of this review is to summarize the current evidence with respect to imaging and specifically mpMRI in planning robot-assisted radical prostatectomy. RECENT FINDINGS: Novel tools integrating mpMRI and clinical data have been described for planning surgery. mpMRI results in adds value to models based on clinical parameters only. Three-dimensional printed models of the prostate and prostatic tumor may help in planning surgery, however only few studies with limited number of patients are currently available in this regard. Finally, the integration of mpMRI renderings in the robotic console may help in surgical planning and might increase the diffusion of imaging for planning (and performing) surgery. SUMMARY: Imaging in planning surgery is still underutilized. Thus, further studies are needed to increase the use of mpMRI in planning surgery and also in performing surgery.

Novel nomogram for the prediction of seminal vesicle invasion including multiparametric magnetic resonance imaging.

OBJECTIVES: To create a model that predicts side-specific seminal vesicle invasion using clinical, biopsy and multiparametric magnetic resonance imaging data. METHODS: We analyzed data from 544 patients who underwent robot-assisted radical prostatectomy at a single institution. To develop a side-specific predictive model, we ultimately considered four variables: prostate-specific antigen, highest ipsilateral biopsy Gleason grade, highest ipsilateral percentage core involvement and seminal vesicle invasion on multiparametric magnetic resonance imaging. A binary multivariable logistic regression model was fitted to predict seminal vesicle invasion. A nomogram was then built based on the coefficients of the resulting logit function. The leave-one-out cross validation method was used for internal validation, and the decision curve analysis for the evaluation of the net clinical benefit. RESULTS: We relied on 804 side-specific cases after excluding negative biopsy observations (n = 284). Seminal vesicle invasion was reported on multiparametric magnetic resonance imaging in 41 (5%) cases, and on final pathology in 64 (8%) cases. All variables in the model emerged as predictors of seminal vesicle invasion (all P ≤ 0.001) and were subsequently considered to build a nomogram. The area under the curve of multiparametric magnetic resonance imaging alone in predicting seminal vesicle invasion was 59.1%; whereas one of the clinical variables only was 85.1%. The area under the curve of the nomogram resulting from their combination was 86.5%. After internal validation, this resulted in 84.7%. The model achieved good calibration and the decision curve analysis showed its clinical benefit, especially when compared with relying only on multiparametric magnetic resonance imaging prediction of seminal vesicle invasion. CONCLUSIONS: A nomogram based on clinical and multiparametric magnetic resonance imaging data can predict seminal vesicle invasion and serve as a tool to urologists for surgical planning.

Development and internal validation of a side-specific, multiparametric magnetic resonance imaging-based nomogram for the prediction of extracapsular extension of prostate cancer.

OBJECTIVES: To develop a nomogram for predicting side-specific extracapsular extension (ECE) for planning nerve-sparing radical prostatectomy. MATERIALS AND METHODS: We retrospectively analysed data from 561 patients who underwent robot-assisted radical prostatectomy between February 2014 and October 2015. To develop a side-specific predictive model, we considered the prostatic lobes separately. Four variables were included: prostate-specific antigen; highest ipsilateral biopsy Gleason grade; highest ipsilateral percentage core involvement; and ECE on multiparametric magnetic resonance imaging (mpMRI). A multivariable logistic regression analysis was fitted to predict side-specific ECE. A nomogram was built based on the coefficients of the logit function. Internal validation was performed using 'leave-one-out' cross-validation. Calibration was graphically investigated. The decision curve analysis was used to evaluate the net clinical benefit. RESULTS: The study population consisted of 829 side-specific cases, after excluding negative biopsy observations (n = 293). ECE was reported on mpMRI and final pathology in 115 (14%) and 142 (17.1%) cases, respectively. Among these, mpMRI was able to predict ECE correctly in 57 (40.1%) cases. All variables in the model except highest percentage core involvement were predictors of ECE (all P ≤ 0.006). All variables were considered for inclusion in the nomogram. After internal validation, the area under the curve was 82.11%. The model demonstrated excellent calibration and improved clinical risk prediction, especially when compared with relying on mpMRI prediction of ECE alone. When retrospectively applying the nomogram-derived probability, using a 20% threshold for performing nerve-sparing, nine out of 14 positive surgical margins (PSMs) at the site of ECE resulted above the threshold. CONCLUSION: We developed an easy-to-use model for the prediction of side-specific ECE, and hope it serves as a tool for planning nerve-sparing radical prostatectomy and in the reduction of PSM in future series.

Inflammation and Prostate Cancer.

Chronic inflammation resulting from infections, altered metabolism, inflammatory diseases or other environmental factors can be a major contributor to the development of several types of cancer. In fact around 20% of all cancers are linked to some form of inflammation. Evidence gathered from genetic, epidemiological and molecular pathological studies suggest that inflammation plays a crucial role at various stages of prostatic carcinogenesis and tumor progression. These include initiation, promotion, malignant conversion, invasion, and metastasis. Detailed basic and clinical research in these areas, focused towards understanding the etiology of prostatic inflammation, as well as the exact roles that various signaling pathways play in promoting tumor growth, is critical for understanding this complex process. The information gained would be useful in developing novel therapeutic strategies such as molecular targeting of inflammatory mediators and immunotherapy-based approaches.

Real-time in vivo periprostatic nerve tracking using multiphoton microscopy in a rat survival surgery model: a promising pre-clinical study for enhanced nerve-sparing surgery.

OBJECTIVES: To assess the ability of multiphoton microscopy (MPM) to visualise, differentiate and track periprostatic nerves in an in vivo rat model, mimicking real-time imaging in humans during RP and to investigate the tissue toxicity and reproducibility of in vivo MPM on prostatic glands in the rat after imaging and final histological correlation study. MATERIALS AND METHODS: In vivo prostatic rat imaging was carried out using a custom-built bench-top MPM system generating real-time three-dimensional histological images, after performing survival surgery consisting of mini-laparotomies under xylazine/ketamine anaesthesia exteriorising the right prostatic lobe. The acquisition time and the depth of anaesthesia were adjusted for collecting multiple images in order to track the periprostatic nerves in real-time. The rats were then monitored for 15 days before undergoing a new set of imaging under similar settings. After humanely killing the rats, their prostates were submitted for routine histology and correlation studies. RESULTS: In vivo MPM images distinguished periprostatic nerves within the capsule and the prostatic glands from fresh unprocessed prostatic tissue without the use of exogenous contrast agents or biopsy sample. Real-time nerve tracking outlining the prostate was feasible and acquisition was not disturbed by motion artefacts. No serious adverse event was reported during rat monitoring; no tissue damage due to laser was seen on the imaged lobe compared with the contralateral lobe (control) allowing comparison of their corresponding histology. CONCLUSIONS: For the first time, we have shown that in vivo tracking of periprostatic nerves using MPM is feasible in a rat model. Development of a multiphoton endoscope for intraoperative use in humans is currently in progress and must be assessed.

Organ-confined prostate cancer: are we moving towards more or less radical surgical intervention?

Treatment possibilities for clinically localised prostate cancer include radical prostatectomy (RP), external beam radiotherapy, brachytherapy, focal therapy and active surveillance. Conflicting and methodologically flawed observational data from the last two decades have led to uncertainty as to the best oncological option. However, recently, there has been a series of high-quality studies that point to disease specific and overall survival advantages for those men undergoing RP. This article reviews the latest evidence and argues that at the current time, RP must be considered the gold standard treatment for the majority of men with clinically localised prostate cancer.