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.
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•The exRNA Atlas provides access to human exRNA profiles and web-accessible tools•Atlas analysis reveals six exRNA cargo types present across five human biofluids•Five of the cargo types associate with specific vesicular and non-vesicular carriers•These findings and resources empower studies of extracellular RNA communication
An extracellular RNA atlas from five human biofluids (serum, plasma, cerebrospinal fluid, saliva, and urine) reveals six extracellular RNA cargo types, including both vesicular and non-vesicular carriers.
The extensive heterogeneity of prostate cancer (PCa) and multilayered complexity of progression to castration-resistant prostate cancer (CRPC) have contributed to the challenges of accurately ...monitoring advanced disease. Profiling of the tumor microenvironment with large-scale transcriptomic studies have identified gene signatures that predict biochemical recurrence, lymph node invasion, metastases, and development of therapeutic resistance through critical determinants driving CRPC.
This review encompasses understanding of the role of different molecular determinants of PCa progression to lethal disease including the phenotypic dynamic of cell plasticity, EMT-MET interconversion, and signaling-pathways driving PCa cells to advance and metastasize. The value of liquid biopsies encompassing circulating tumor cells and extracellular vesicles to detect disease progression and emergence of therapeutic resistance in patients progressing to lethal disease is discussed. Relevant literature was added from PubMed portal.
Despite progress in the tumor-targeted therapeutics and biomarker discovery, distant metastasis and therapeutic resistance remain the major cause of mortality in patients with advanced CRPC. No single signature can encompass the tremendous phenotypic and genomic heterogeneity of PCa, but rather multi-threaded omics-derived and phenotypic markers tailored and validated into a multimodal signature.
Prostate cancer is the second most common cancer in men worldwide and causes over 250,000 deaths each year. Overtreatment of indolent disease also results in significant morbidity. Common genetic ...alterations in prostate cancer include losses of NKX3.1 (8p21) and PTEN (10q23), gains of AR (the androgen receptor gene) and fusion of ETS family transcription factor genes with androgen-responsive promoters. Recurrent somatic base-pair substitutions are believed to be less contributory in prostate tumorigenesis but have not been systematically analyzed in large cohorts. Here, we sequenced the exomes of 112 prostate tumor and normal tissue pairs. New recurrent mutations were identified in multiple genes, including MED12 and FOXA1. SPOP was the most frequently mutated gene, with mutations involving the SPOP substrate-binding cleft in 6-15% of tumors across multiple independent cohorts. Prostate cancers with mutant SPOP lacked ETS family gene rearrangements and showed a distinct pattern of genomic alterations. Thus, SPOP mutations may define a new molecular subtype of prostate cancer.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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.
What's known on the subject? and What does the study add?
During radical prostatectomy, urological surgeons have tried to identify the “cord‐like NVB” at the lateral aspect of the prostate. However, ...little histological or physiological investigation was conducted to verify that the NVB identified at surgery really included the cavernous nerve. Recently, there have been observations that refute the dogma that the cavernous nerve is always within the NVB.
In this study, we have described a hammock‐like distribution of the nerves on which the prostate rests, demonstrating that the NVB is more a network of multiple fine dispersed nerves than a distinct structure. We presented a novel nerve‐sparing approach to complete hammock preservation. This risk‐stratified approach for determining the degree of nerve sparing based on the patient's likelihood of ipsilateral EPE seeks to categorize patients for optimal balance between oncological outcomes and functional outcomes.
OBJECTIVES
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To report the potency and oncological outcomes of patients undergoing robot‐assisted radical prostatectomy (RARP) using a risk‐stratified approach based on layers of periprostatic fascial dissection.
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We also describe the surgical technique of complete hammock preservation or nerve sparing grade 1.
PATIENTS AND METHODS
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This is a retrospective study of 2317 patients who had robotic prostatectomy by a single surgeon at a single institution between January 2005 and June 2010.
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Included patients were those with ≥1 year of follow‐up and who were potent preoperatively, defined as having a sexual health inventory for men (SHIM) questionnaire score of >21; thus, the final number of patients in the study cohort was 1263.
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Patients were categorized pre‐operatively by a risk‐stratified approach into risk grades 1–4, where risk grade 1 patients received nerve‐sparing grade 1 or complete hammock preservation and so on for risk grades 2–4, as long as intraoperative findings permitted the planned nerve sparing.
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We considered return to sexual function post‐operatively by two criteria: i) ability to have successful intercourse (score of ≥4 on question 2 of the SHIM) and ii) SHIM >21 or return to baseline sexual function.
RESULTS
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There was a significant difference across different NS grades in terms of the percentages of patients who had intercourse and returned to baseline sexual function (P < 0.001), with those that underwent NS grade 1 having the highest rates (90.9% and 81.7%) as compared to NS grades 2 (81.4% and74.3%), 3 (73.5% and 66.1%), and 4 (62% and 54.5%).
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The overall positive surgical margin (PSM) rates for patients with NS grades 1, 2, 3, and 4 were 9.9%, 8.1%, 7.2%, and 8.7%, respectively (P = 0.636).
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The extraprostatic extension rates were 11.6%, 14.3%, 29.3%, and 36.2%, respectively (P < 0.001).
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Similarly, in patients younger than 60, intercourse and return to baseline sexual function rates were 94.9% and 84.3% for NS grade 1 as compared to 85.5% and 77.2% for NS grades 2, 76.9% and 69% for NS grades 3, and 64.8% and 57.7% for NS Grade 4 (P < 0.001).
CONCLUSIONS
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The risk‐stratified approach and anatomical technique of neural‐hammock sparing described in the present manuscript was effective in improving potency outcomes of patients without compromising cancer control.
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Patients with greater degrees of NS had higher rates of intercourse and return to baseline sexual function without an increase in PSM rates.
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.
Background
The field of robotic surgery has seen significant advancements in the past few years and it has been adopted in many large hospitals in the United States and worldwide as a standard for ...various procedures in recent years. However, the location of many hospitals in urban areas and a lack of surgical expertise in the rural areas could lead to increased travel time and treatment delays for patients in need of robotic surgical management, including cancer patients. The fifth generation (5G) networks have been deployed by various telecom companies in multiple countries worldwide. Our aim is to update the readers about the novel technology and the current scenario of surgical procedures performed using 5G technology. In this article, we also discuss how the technology could aid cancer patients requiring surgical management, the future perspectives, the potential challenges, and the limitations, which would need to overcome prior to widespread real‐life use of the technology for cancer care.
Recent findings
The expansion of 5G technology has enabled some countries to conduct remote surgical procedures, tele‐mentored and real‐time interactive procedures on animal models, cadavers, and humans, demonstrating that 5G networks could offer a potential solution to previously experienced latency and reliability hurdles during the remote surgeries performed in the 2000s.
Conclusion
New technological advancements could serve as a ground for emerging novel therapeutic applications. While limitations and challenges related to the 5G infrastructure, cost, compatibility, and security exist; researching to overcome the limitations and comprehend the potential benefits of integrating the technology into practice would be imminent before widespread clinical use. Remote and tele‐mentored 5G‐powered procedures could offer a new tool in improving the care of patients requiring robotic surgical management such as prostate cancer patients.
To examine female author representation within publications in the field of urology from the United States from 2000-2019.
All 25,787 articles with a U.S. correspondence address published in the two ...largest U.S. headquartered general urology journals, Urology and Journal of Urology, were analyzed from 2000-2019. Gender was assigned to each first and last author based on the author's first name. First names were matched to a database of U.S. Social Security Administration data to determine gender.
Overall female authorship, female senior authorship, and female first authorship exhibited a significant upward trend from 2000 to 2019 (P <0.001, P <0.001, P = 0.002). As the number of female last authors increased, female last authors were significantly more likely to publish with female first authors, and significantly less likely publish with male first authors (P <0.001, P <0.001). Furthermore, we found a significant difference for female authors being less likely to get cited than male authors (p = 0.02), despite the greater proportion of females that authored research articles with higher citation counts compared to males (P <0.05).
Despite the significant progress in female representation within urological publications, female-authored publications continue to constitute a smaller proportion of the urological literature and are less likely to be cited. Our study provides the first evidence on the current status of female underrepresentation within academic urology and literature productivity at this watershed moment. As the number of female urologists evolves, these findings will be of significant impact in the advancement of female investigators in urology.
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 (
= 695). The expression results of selected connective tissue genes were analyzed after multiple
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
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, and underexpression in
and
. 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% (
= 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.
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