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BACKGROUND: Testicular cancer is a common malignancy among young males in western countries. OBJECTIVE: To examine the global disease burden and trends of testicular cancer incidence and mortality by age and country, and their associations with human development index (HDI), gross domestic product (GDP), lifestyle habits, and metabolic risk factors. DESIGN, SETTING, AND PARTICIPANTS: We retrieved the Global Cancer Observatory database for the testicular cancer incidence and mortality in 2020; the World Bank for GDP per capita; the United Nations for HDI; the WHO Global Health Observatory for prevalence of smoking and alcohol drinking; and the Cancer Incidence in Five Continents, WHO mortality database, Surveillance, Epidemiology, and End Results programme and Nordic Cancer Registries (NORDCAN) for trend analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We presented the testicular cancer incidence and mortality using age-standardised rates. We examined their associations with HDI, GDP, smoking, alcohol drinking, physical inactivity, overweight, obesity, and medical conditions including diabetes, hypertension, and hypercholesterolaemia by linear regression. We estimated the 10-yr trend of incidence and mortality by joinpoint regression with average annual percentage change with 95% confidence intervals in different age groups. RESULTS AND LIMITATIONS: There was a wide variation in the testicular cancer burden with the highest mortality found in low-income countries, and the regions of Central America and South America, while the highest incidence was observed in high-income countries, especially in Western and Northern Europe. We found a positive association for HDI, GDP, alcohol drinking, inactivity, overweight, obesity, and hypercholesterolaemia with testicular cancer incidence, while a negative correlation was observed between GDP and mortality of testicular cancer. Globally, there was an overall increasing incidence trend of testicular cancer for the past decade, particularly in younger males; the mortality trends of testicular cancer were relatively stable. However, we did not analyse the trend of different stages and subtypes of testicular cancer due to data unavailability. CONCLUSIONS: There was a global variation in the testicular cancer burden associated with HDI, GDP, alcohol drinking, inactivity, overweight, obesity, and hypercholesterolaemia. Testicular cancer had an increasing incidence but decreasing mortality. The increasing testicular cancer incidence in the younger population is of concern and calls for early detection and preventive interventions. PATIENT SUMMARY: Globally, testicular cancer incidence had been increasing particularly in the younger population, although its deaths rates had been decreasing. Socioeconomic indices, alcohol drinking, inactivity, overweight, obesity, and high plasma lipid levels are associated with testicular cancer incidence and mortality.

Objectives To investigate the outcome of retzius-sparing robotic-assisted radical prostatectomy (RS-RARP) compared with conventional RARP in the early learning curve. Methods Consecutive patients with prostate cancer who underwent RS-RARP were included to compare against conventional RARP of the same period. Propensity-score matching was performed based on age, prostate size, nerve-sparing approach, and final pathological risk categories. All patients were re-admitted to undergo trial without Foley catheter from post-operative day 7-10. Clinical follow-up was performed with monitoring of continence (day 0, 3 months, and the latest continence during the study period) and surveillance of PSA level. Results Between July 2017 and August 2019, 24 consecutive patients received RS-RARP in our centre. Propensity score matching was performed with the best matched 24 controls receiving conventional RARP. Overall median follow-up duration was 15.5 months. A majority of the patients belonged to the intermediate-risk group, with most of them harbouring pT2 disease (RS-RARP: 87.5%; conventional RARP: 79.2%). More patients in RS-RARP group achieved day-0 continence (33.3% vs 0%, p = 0.002) and 3-month continence (66.7% vs 12.5%, p = 0.001). During the whole study period, more RS-RARP achieved continence with 0 pad (91.7% vs 66.7%, p = 0.033). The mean months to continence is shorter in RS-RARP group (4.0 months vs 13.6 months, p = 0.002). No statistically significant differences between the two groups with respect to surgical margins, post-operative PSA detection, and the use of adjuvant radiotherapy. Conclusions RS-RARP showed better continence rates when compared to conventional RARP even during the learning curve phase.

Purpose of review To investigate the features and optimal management of pN+ cM0 prostate cancer (PCa) according to registry-based studies. Recent findings Up to 15% of PCa patients harbor lymph node invasion (pN+) at radical prostatectomy plus lymph node dissection. Nonetheless, the optimal management strategy in this setting is not well characterized. Summary We performed a systematic review including n = 13 studies. Management strategies comprised 13 536 men undergoing observation, 11 149 adjuvant androgen deprivation therapy (aADT), 7,075 adjuvant radiotherapy (aRT) +aADT and 705 aRT. Baseline features showed aggressive PCa in the majority of men. At a median follow-up ranging 48-134months, Cancer-related death was 5% and overall-mortality 16.6%. aADT and aRT alone had no cancer-specific survival or overall survival advantages over observation only and over not performing aRT, respectively. aADT plus aRT yielded a survival benefit compared to observation and aADT, which in one study, were limited to certain intermediate-risk categories. Age, Gleason, Charlson score, positive surgical margins, pathological stage, and positive nodes number, but not prostate specific antigen, were most relevant prognostic factors. Our work further confirmed pN+ PCa is a multifaceted disease and will help future research in defining its optimal management based on different risk categories to maximize survival and patient's quality of life.

Purpose:We performed a systematic review comparing the incidence of infectious complications following transperineal ultrasound-guided prostate biopsy (TPB) in cases utilizing antibiotic prophylaxi...

Background: Although China accounts for 7.8% of worldwide new prostate cancer (PCa) cases and 14.5% of new deaths according to GLOBOCAN 2020, the risk of PCa associated with germline mutations is poorly defined, hampered in part by lack of nationwide evidence. Here, we sequenced 19 PCa predisposition genes in 1,836 Chinese patients with PCa and estimated disease risk associated with inherited mutations. Patients and Methods: Patients were recruited from 4 tertiary cancer centers (n=1,160) and a commercial laboratory (n=676). Germline DNA was sequenced using a multigene panel, and pathogenic/likely pathogenic (P/LP) mutation frequencies in patients with PCa were compared with populations from the gnomAD (Genome Aggregation Database) and ChinaMAP (China Metabolic Analytics Project) databases. Clinical characteristics and progression-free survival were assessed by mutation status. Results: Of 1,160 patients from hospitals, 89.7% had Gleason scores ≥8, and 65.6% had metastases. P/LP mutations were identified in 8.49% of Chinese patients with PCa. Association with PCa risk was significant for mutations in ATM (odds ratio [OR], 5.9; 95% CI, 3.1–11.1), BRCA2 (OR, 15.3; 95% CI, 10.0–23.2), MSH2 (OR, 15.8; 95% CI, 4.2–59.6), and PALB2 (OR, 5.9; 95% CI, 2.7–13.2). Compared with those without mutations, patients with mutations in ATM, BRCA2, MSH2, or PALB2 showed a poor outcome with treatment using androgen deprivation therapy and abiraterone (hazard ratio, 2.19 [95% CI, 1.34–3.58] and 2.47 [95% CI, 1.23–4.96], respectively) but similar benefit from docetaxel. Conclusions: The present multicenter study confirmed that a significant proportion of Chinese patients with PCa had inherited mutations and identified predisposition genes in this underreported ethnicity. These data provide empirical evidence for precision prevention and prognostic estimation in Chinese patients with PCa.

BACKGROUND: We aimed to investigate perineal nerve block versus periprostatic block in pain control for men undergoing a transperineal prostate biopsy. METHODS: In this prospective, randomised, blinded and parallel-group trial, men in six Chinese hospitals with suspected prostate cancer were randomly assigned (1:1) at the point of local anaesthesia to receive a perineal nerve block or periprostatic block and followed by a transperineal prostate biopsy. Centres used their usual biopsy procedure. Operators who performed anaesthesia were trained in both techniques before the trial and were masked to the randomised allocation until the time of anaesthesia and were not involved in the subsequent biopsy procedure and any assessment or analysis. Other investigators and the patients were masked until trial completion. The primary outcome was the level of the worst pain experienced during the prostate biopsy procedure. Secondary outcomes included pain (post-biopsy at 1, 6 and 24 h), changes in blood pressure, heart rate and breathing rate during the biopsy procedure, external manifestations of pain during biopsy, anaesthesia satisfaction, the detection rate of PCa and clinically significant PCa. This trial is registered on ClinicalTrials.gov, NCT04501055. FINDINGS: Between August 13, 2020, and July 20, 2022, 192 men were randomly assigned to perineal nerve block or periprostatic block, 96 per study group. Perineal nerve block was superior for the relief of pain during the biopsy procedure (mean 2.80 for perineal nerve block and 3.98 for periprostatic block; adjusted difference in means −1.17, P

Background: We aimed to examine the global disease burden and trends of prostate cancer incidence and mortality by age, and their associations with gross domestic product (GDP), human development index (HDI), smoking, and alcohol drinking. Materials and Methods: We retrieved the Global Cancer Observatory (GLOBOCAN) database for the incidence and mortality of prostate cancer in 2020; the World Bank for GDP per capita; the United Nations for HDI; the WHO Global Health Observatory for prevalence of smoking and alcohol drinking; the Cancer Incidence in 5 Continents (CI5), WHO mortality database, for trend analysis. We presented the prostate cancer incidence and mortality using age-standardized rates. We examined their associations with GDP, HDI, smoking, and alcohol drinking by Spearman's correlations and multivariable regression. We estimated the 10-year trend of incidence and mortality by joinpoint regression analysis with average annual percent change with 95% confidence intervals in different age groups. Results: A wide variation in the burden of prostate cancer with the highest mortality found in low-income countries while the highest incidence was observed in high-income countries. We found moderate to high positive correlations for GDP, HDI, and alcohol drinking with prostate cancer incidence, whilst a low negative correlation was observed for smoking. Globally, there was an increasing incidence but decreasing mortality of prostate cancer, and such trends were particularly prominent in Europe. Notably, the incidence increase was also found in the younger population aged

To assess the degree of psychological impact among surgical providers during the COVID-19 pandemic.The COVID-19 pandemic has extensively impacted global healthcare systems. We hypothesized that the degree of psychological impact would be higher for surgical providers deployed for COVID-19 work, certain surgical specialties, and for those who knew of someone diagnosed with, or who died, of COVID-19.We conducted a global web-based survey to investigate the psychological impact of COVID-19. The primary outcomes were the Depression Anxiety Stress Scale-21 (DASS-21) and Impact of Event Scale-Revised (IES-R) scores.4283 participants from 101 countries responded. 32.8%, 30.8%, 25.9% and 24.0% screened positive for depression, anxiety, stress and Post-Traumatic Stress Disorder (PTSD) respectively. Respondents who knew someone who died of COVID-19 were more likely to screen positive for depression, anxiety, stress and PTSD (OR 1.3, 1,6, 1.4, 1.7 respectively, all p0.05). Respondents who knew of someone diagnosed with COVID-19 were more likely to screen positive for depression, stress and PTSD (OR 1.2, 1.2 and 1.3 respectively, all p0.05). Surgical specialities that operated in the Head and Neck region had higher psychological distress among its surgeons. Deployment for COVID-19-related work was not associated with increased psychological distress.The COVID-19 pandemic may have a mental health legacy outlasting its course. The long-term impact of this ongoing traumatic event underscores the importance of longitudinal mental health care for healthcare personnel, with particular attention to those who know of someone diagnosed with, or who died of COVID-19.

Urological cancers are common malignancies worldwide. Several conventional models, for example, two-dimensional cell culture and animal models have been used for decades to study tumor genetics. Nonetheless, these methods have limitations in reflecting the real tumor microenvironment in vivo, thereby hindering the development of anti-cancer therapeutic agents. Recently, three-dimensional culture models have gained attention because they can overcome the drawbacks of traditional methods. Above all, three-dimensional organoid models are able to mimic the tumor microenvironment in human bodies more closely as they are able to demonstrate the interactions between cells and extracellular matrix. This type of model has therefore extended our understanding of urological cancers. Tumor cells in organoid models can also be co-cultured with other cellular components, such as peripheral blood lymphocytes, and allow further understanding of the effect of tumor microenvironments on tumor growth. Furthermore, organoid models allow a prolonged culturing period, therefore, tumor evolution, progression and maintenance can also be assessed. Organoid models can be derived from each specific patient, and this facilitates investigation of individual cancer-specific mutations and their subtypes. As a result, the development of personalized medication targeting the signaling pathways or biomolecules of interest will be possible. In the present review, we summarize the development and applications of three-dimensional organoid cultures in urological cancers, mainly focusing on prostate, urinary bladder and kidney cancers, and assess the future prospects of this model.

Background: Men with elevated prostate-specific antigen (PSA) and initial negative prostate biopsy may have risk of prostate cancer (PCa) in the future. The role of Prostate Health Index (phi) in determining future PCa risk has not been studied before. This study aims to investigate the role of initial phi and phi density in predicting future PCa risk in men with initial negative biopsy. Methods: Five hundred sixty nine men with PSA 4–10 ng/mL were recruited between 2008 and 2015 for prostate biopsy with prior phi. Electronic clinical record of men with initial negative biopsy was reviewed. Patients and follow-up doctors were blinded to phi. Kaplan–Meier curves were used to analyze the PCa-free survival in different baseline phi and phi density groups. Results: Four hundred sixty-one men with complete follow-up data were included. Median follow-up is 77 months. PCa and HGPCa was diagnosed in 8.2% (38/461) and 4.8% (22/461) of cohort respectively. A higher baseline phi value was associated with PCa (p = 0.003) and HGPCa (p < 0.001). HGPCa was diagnosed in 0.6% (1/163) of phi < 25, 4.6% (9/195) of phi 25–34.9, and 11.7% (12/103) of phi ≥ 35 (p < 0.001). HGPCa was diagnosed in 0% (0/109) and 21.0% (13/62) with phi density of

To investigate the value of machine learning(ML) in enhancing prostate cancer(PCa) diagnosis. Consecutive systematic prostate biopsies performed from Jan 2003–June 2017 were used as the training cohort, and prospective biopsies performed from July 2017-November 2019 were used as validation cohort. Men were included if PSA was 0.4–50 ng/mL, and information of digital rectal examination (DRE), Transrectal ultrasound(TRUS) prostate volume, TRUS abnormality were known. Clinically significant PCa(csPCa) was defined as Gleason 3 + 4 or above cancers. Area-under-curve (AUC) of receiver-operating characteristics (ROC) was compared between PSA, PSA density, European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator (ERSPC-RC), and various ML techniques using PSA, DRE and TRUS information. ML techniques used included XGBoost, LightGBM, Catboost, Support vector machine (SVM), Logistic regression (LR), and Random Forest (RF), where cost sensitive learning was applied. Training and validation cohorts included 3881 and 778 consecutive men, respectively. RF model performed better than other ML techniques and PSA, PSA density and ERSPC-RC for prediction of PCa or csPCa in the validation cohort. In csPCa prediction, AUC of PSA, PSA density, ERSPC-RC and RF was 0.71, 0.80, 0.83 and 0.88 respectively. At 90–95% sensitivity for csPCa, RF model achieved a negative predictive value (NPV) of 97.5–98.0% and avoided 38.3–52.2% unnecessary biopsies. Decision curve analyses (DCA) showed RF model provided net clinical benefit over PSA, PSA density and ERSPC-RC. By using the same clinical parameters, ML techniques performed better than ERSPC-RC or PSA density in csPCa predictions, and could avoid up to 50% unnecessary biopsies.

This study investigates whether the application of Hemopatch, a novel hemostatic patch, could prevent lymphatic leak after robotic-assisted radical prostatectomy (RARP) and bilateral pelvic lymph node dissection (BPLND). This is a prospective, single-center, phase III randomized controlled trial investigating the efficacy of Hemopatch in preventing lymphatic leak after RARP and BPLND. Participants were randomized to receive RARP and BPLND, with or without the use of Hemopatch, with an allocation ratio of 1:1. The primary outcome is the total drain output volume. The secondary outcomes include blood loss, operative time, lymph node yield, duration of drainage, drain output per day, hospital stay, transfusion and 30-day complications. A total of 32 patients were recruited in the study. The Hemopatch group had a significantly lower median total drain output than the control group (35 mL vs. 180 mL, p = 0.022) and a significantly lower drain output volume per day compared to the control group (35 mL/day vs. 89 mL/day, p = 0.038). There was no significant difference in the other secondary outcomes. In conclusion, the application of Hemopatch in RARP and BPLND could reduce the total drain output volume and the drain output volume per day. The use of Hemopatch should be considered to prevent lymphatic leakage after RARP and BPLND.

Urine proteome is a valuable reservoir of biomarkers for disease diagnosis and monitoring. Following its formation as the plasma filtrate in the kidney, urine is progressively modified by the active reabsorption and secretion of the cells lining the urinary tract. However, little is known about how the urine proteome changes as it passes along the urinary tract. To investigate this, we compared the proteome composition of renal pelvis urine (RPU) and individually self-voided bladder urine (BU) collected from 7 one-side urinary tract obstruction male patients. While no exclusive proteins were observed for either type of urine sample, BU had more proteins that were overrepresented at a higher frequency than RPU. Furthermore, the label-free quantitative analysis indicated that the BU proteome has a higher diversity in dominant proteins in conjunction with more upregulated proteins. Functional annotation revealed the BU-RPU differential proteins are enriched in exosomes and extracellular proteins, indicating active urothelial-urinary interactions. These differential proteins can facilitate biomarker discovery for diseases affecting the urinary tract.

Purpose The COVID-19 pandemic has led to the cancellation or deferment of many elective cancer surgeries. We performed a systematic review on the oncological effects of delayed surgery for patients with localised or metastatic renal cell carcinoma (RCC) in the targeted therapy (TT) era. Method The protocol of this review is registered on PROSPERO(CRD42020190882). A comprehensive literature search was performed on Medline, Embase and Cochrane CENTRAL using MeSH terms and keywords for randomised controlled trials and observational studies on the topic. Risks of biases were assessed using the Cochrane RoB tool and the Newcastle–Ottawa Scale. For localised RCC, immediate surgery [including partial nephrectomy (PN) and radical nephrectomy (RN)] and delayed surgery [including active surveillance (AS) and delayed intervention (DI)] were compared. For metastatic RCC, upfront versus deferred cytoreductive nephrectomy (CN) were compared. Results Eleven studies were included for quantitative analysis. Delayed surgery was significantly associated with worse cancer-specific survival (HR 1.67, 95% CI 1.23–2.27, p

Androgen deprivation therapy (ADT), either by medical or surgical castration, is the backbone for standard treatment of locally advanced or metastatic prostate cancer, yet it is also associated with various metabolic and cardiovascular complications. Recent evidence have shown that obesity, insulin resistance, or metabolic disturbances can be associated with changes in the gut microbiome, while animal studies also show that castration is associated with changes in the gut microbiome. This study aims to investigate whether the fecal microbiota in prostate cancer patients who had undergone prostatectomy or ADT are different, and explore changes in phylogeny and pathways that may lead to side effects from ADT. A total of 86 prostate cancer patients (56 patients on ADT and 30 patients with prostatectomy) were recruited. The fecal microbiota was analyzed by the 16S rRNA gene for alpha- and beta-diversities by QIIME2, as well as the predicted metabolic pathways by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2. The alpha-diversity was significantly lower in the ADT group. The beta-diversity was significantly different between the groups, in which Ruminococcus gnavus and Bacteroides spp were having higher relative abundance in the ADT group, whereas Lachnospira and Roseburia were reduced. The Firmicutes-to-Bacteroidetes ratio is noted to be lower in the ADT group as well. The functional pathway prediction showed that the biosynthesis of lipopolysaccharide (endotoxin) and propanoate was enriched in the ADT as well as the energy cycle pathways. This study is limited by the cross-sectional design and the clinical heterogeneity. There is a significant difference in gut microbiome between prostate cancer patients on ADT and prostatectomy. We theorize that this difference may contribute to the development of metabolic complications from ADT. Further longitudinal studies are awaited.

Introduction & Objectives: Spermine (Spm) is a typical metabolite that is highly concentrated in healthy prostate epithelium maintaining cell growth and functions. Our previous studies found that Spm was significantly decreased in PCa tissue than in benign prostate tissue, as was the urinary Spm in PCa. This study aimed to reveal the specific role of Spm in PCa. Materials & Methods: In this study, Spm was resupplied to castration-resistant prostate cancer (CRPC) cells (PC3 and DU145). Following Spm treatment, MTT (methyl thiazolyl tetrazolium) and EdU (5-ethynyl-2’-deoxyuridine) assay were used to determine the cell proliferation of CRPC cell lines. Cellular apoptosis, cell cycle distribution and mitochondrial membrane potential were analyzed by flow cytometry. Cellular reactive Oxygen species (ROS) level was measured by fluorescence microscope. mRNA and ATAC sequencing in spermine-treated CRPC cells were performed to reveal the related mechanism for Spm effect. Results: In the in vitro studies, Spm was found to inhibit the cell viability of CRPC cells. Transwell assays demonstrated that Spm impaired migration and invasion ability. And Spm blocked tumor progression by inducing G2/M arrest and cellular apoptosis in CRPC cells dose-dependently. mRNA seq revealed that a series of genes were altered after Spm treatment and indicated the potential functional pathway of Spm might be mitophagy. We integrated mRNA seq data with ATAC seq profiles and accessed those genes regulated by polyamine metabolism and Spm-induced mitophagy. Results showed the sequencing tracks for the HMOX1 locus contain higher ATAC-seq peaks at the promoter under Spm treatment. Spm could affect oxidative phosphorylation which will lead to mitophagy and mitochondrial metabolism by modulating the transcriptional accessibility of genes. After Spm treatment, cellular ROS was upregulated while the mitochondrial membrane potential collapsed. Subsequently, western blot results showed that PINK1-mediated mitophagy related-proteins were significantly regulated. Conclusion: Our results indicated that Spm treatment led to mitochondrial dysfunction and subsequently degraded through mitophagy in CRPC cells. Our findings could provide a theoretical basis and have preliminary clinical implications in developing Spm as a promising agent against CRPC by inducing cellular mitophagy in CRPC cells. Citation Format: Jingkai Sun, Peter Ka-Fung Chiu, Tingting Xie, Jeremy Yuen-Chun Teoh, Chi-Fai Ng. Investigation the function and application of spermine in castration-resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 520.

Introduction and Objective: Non-coding RNAs (ncRNAs) represent a diverse family of regulatory transcripts that drive tumorigenesis of prostate cancer (PCa) and various other types of cancers by their hyperactivity or diminished function. PIWI-interacting RNAs (piRNAs) are a class of small ncRNAs mechanistically similar to but much less studied than microRNAs. As the most diversified small ncRNAs, piRNAs are widely involved in the pathogenesis of different types of cancers. Our study aimed to investigate the role of piRNAs in the development of castration-resistant prostate cancer (CRPC). Methods: Small RNA sequencing was used to explore the CRPC associated piRNAs on a basis of 10 benign prostate tissues, 10 paired hormone-sensitive PCa tissues and CRPC tissues from the same patients. The top 12 upregulated piRNAs were validated through qRT-PCR in a bigger cohort. piR-hsa-4447944 was selected and investigated its biological function by gain of function in vitro. To study its loss of function role, an androgen-independent PCa cell (LNCaP-AI) was established. For mechanistic investigation, high-throughput RNA sequencing was conducted to identify dysregulated genes in PCa cells with control or piR-hsa-4447944 overexpression. Then, potential downstream targets were further predicted by miRanda program and validated by qRT-PCR, western-blot and dual-luciferase reporter assay. Results: piR-hsa-4447944 demonstrated a relatively higher expression level in both CRPC tissues and CRPC cell lines when compared with PCa tissues and cells. Functionally, overexpression of piR-hsa-4447944 could confer resistance to androgen deprivation and anti-androgen in PCa cells in vitro, whereas anti-sense RNA against the piR-hsa-4447944 could potentiate the sensitivity to androgen deprivation in LNCaP-AI cell. In addition, piR-hsa-4447944 showed the ability in promoting migration and invasion of PCa cells. Mechanistically, mRNA sequencing results identified a panel of downstream target-genes. Among them, neurofilament heavy chain (NEFH) was predicted and validated to have a direct binding relationship with piR-hsa-4447944, and was successfully verified to be negatively regulated by piR-hsa-4447944 in PCa cells. Conclusions: Our study showed, for the first time, that piR-hsa-4447944 can contribute to androgen insensitivity in CRPC. This sheds a new insight into the regulation of CRPC by a small ncRNA piRNA, which may form the basis of a novel target in the treatment of CRPC. Citation Format: Qiang Peng, Jingkai Sun, Peter Ka-Fung Chiu, Tingting Xie, Jeremy Yuen-Chun Teoh, Chi-Fai Ng. PiR-hsa-4447944 promotes the progression of prostate cancer through NEFH and induces androgen-independent growth. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3771.

BackgroundDouble-stranded DNA in plasma is known to carry single-stranded ends, called jagged ends. Plasma DNA jagged ends are biomarkers for pathophysiologic states such as pregnancy and cancer. It remains unknown whether urinary cell-free DNA (cfDNA) molecules have jagged ends.MethodsJagged ends of cfDNA were detected by incorporating unmethylated cytosines during a DNA end-repair process, followed by bisulfite sequencing. Incorporation of unmethylated cytosines during the repair of the jagged ends lowered the apparent methylation levels measured by bisulfite sequencing and were used to calculate a jagged end index. This approach is called jagged end analysis by sequencing.ResultsThe jagged end index of urinary cfDNA was higher than that of plasma DNA. The jagged end index profile of plasma DNA displayed several strongly oscillating major peaks at intervals of approximately 165 bp (i.e., nucleosome size) and weakly oscillating minor peaks with periodicities of approximately 10 bp. In contrast, the urinary DNA jagged end index profile showed weakly oscillating major peaks but strongly oscillating minor peaks. The jagged end index was generally higher in nucleosomal linker DNA regions. Patients with bladder cancer (n = 46) had lower jagged end indexed of urinary DNA than participants without bladder cancer (n = 39). The area under the curve for differentiating between patients with and without bladder cancer was 0.83.ConclusionsJagged ends represent a property of urinary cfDNA. The generation of jagged ends might be related to nucleosomal structures, with enrichment in linker DNA regions. Jagged ends of urinary DNA could potentially serve as a new biomarker for bladder cancer detection.

As the conventional workup for diagnosing prostate cancer, transrectal systematic biopsy carries the risk of sepsis and overdiagnosis of insignificant prostate cancer. In recent years, multiparametric MRI (mpMRI) has revolutionized the diagnostic approach to prostate cancer. With widespread use of the prostate imaging and data system (PIRADS), MRI reporting has been more standardized. Several landmark papers have indicated that mpMRI in combination with targeted or combined biopsy can confidently diagnose more clinically significant prostate cancer while reducing diagnoses of insignificant disease. In this review, we aim to discuss the advantages of pre-biopsy MRI based on the current literature and to address its reliability in ruling out prostate cancer, reproducibility, and cost-effectiveness.

BACKGROUND: Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) are closely related. The effect of AKI on the clinical outcomes of these two conditions is unclear. METHODS: This retrospective, territory-wide cohort study used an electronic public healthcare database in Hong Kong to identify patients with SARS or COVID-19 by diagnosis codes, virologic results, or both. The primary endpoint was a composite of intensive care unit admission, use of invasive mechanical ventilation, and/or death. RESULTS: We identified 1670 patients with SARS and 1040 patients with COVID-19 (median ages, 41 versus 35 years, respectively). Among patients with SARS, 26% met the primary endpoint versus 5.3% of those with COVID-19. Diabetes mellitus, abnormal liver function, and AKI were factors significantly associated with the primary endpoint among patients with either SARS or COVID-19. Among patients with SARS, 7.9%, 2.1%, and 3.7% developed stage 1, stage 2, and stage 3 AKI, respectively; among those with COVID-19, 6.6%, 0.4%, and 1.1% developed stage 1, stage 2, and stage 3 AKI, respectively. In both groups, factors significantly associated with AKI included diabetes mellitus and hypertension. Among patients with AKI, those with COVID-19 had a lower rate of major adverse clinical outcomes versus patients with SARS. Renal function recovery usually occurred within 30 days after an initial AKI event. CONCLUSIONS: AKI rates were higher among patients with SARS than those with COVID-19. AKI was associated with major adverse clinical outcomes for both diseases. Patients with diabetes mellitus and abnormal liver function were also at risk of developing severe consequences after SARS and COVID-19 infection.

We conducted a systematic review of the literature on primary clear cell carcinoma (CCC) of the urinary bladder. A literature search using keywords and MeSH terms related to “clear cell carcinoma”, “clear cell adenocarcinoma”, “mesonephroma” and “urinary bladder” in EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials was performed. A manual search was performed with web-based search engine Google Scholar. Reference lists of the included studies were screened for additional articles. Articles up till 16th July 2020 were retrieved. Observational human studies on primary CCC in urinary bladder with English full-text were included for further analysis. 904 articles were identified and 44 articles were included for further analysis. Data including clinical features, tumour characteristics, treatment and oncological outcomes were reviewed. There were 70 patients (44 females and 26 males) reported in literatures and included in this review. Gross haematuria was the most common presentation (79.7%), followed by irritative urinary symptoms (47.5%). Regarding the histology, tubulocystic pattern is the most common histologic pattern (49.1%), and 52.6% had muscle invasion. Most cases were CK7 (96.6%) and CK20 (88.9%) positive. CA125 (96%) was commonly positive, indicating its potential origin from mullerian duct. Most patients received surgery (95.5%) as primary treatment. However, the oncological outcomes were unsatisfactory with a 2-year survival rate of 60.0%. Clear cell carcinoma is an uncommon subtype of bladder cancer which can be diagnosed by histology and immunohistochemical staining result. The majority of patients presented with muscle invasion and had a poor survival despite aggressive treatment.

BackgroundTo investigate the efficacy of transperineal targeted microwave ablation (TMA) in treating localized prostate cancer (PCa). MethodsThis is a single-centre prospective phase 2 trial recruiting men with low to intermediate risk localized PCa to undergo transperineal TMA. TMA was performed with MRI-Ultrasound fusion guidance and organ-based tracking. A per-protocol 6-month MRI and biopsy was performed for all patients. The primary outcome was any cancer detected on biopsy of each ablated area. Secondary outcomes included per-patient analysis of positive biopsy, complications, urinary symptom score, erectile function and quality of life (QOL) scores. ResultsIn the first 15 men, 23 areas were being treated. The median age was 70 years, number of TMA ablations were 5 (range 2-8), and the total ablation time and operating time was 22 (IQR 14-28) and 75 (IQR 65-85) minutes, respectively. PSA level dropped from a median of 7.7 to 2.4 ng/mL. For the primary outcome, 91.3% (21/23) ablated area had no cancer in 6-month biopsy. In per-patient analysis, 33.3% (5/15) had in or out-of-field positive biopsy at 6 months. Among these 5 cases, 4 of them were amenable for active surveillance and 1 (6.7%) case with out-of-field ISUP grade group 2 cancer received radiotherapy. The urinary symptoms, uroflowmetry, erectile function, and QOL scores had no significant difference at 6 months. Grade 1 complications including hematuria (33.3%), dysuria (6.7%), and perineal discomfort (13.4%) were observed. ConclusionsIn this first pilot study, transperineal TMA guided by MRI-Ultrasound fusion guidance and organ-based tracking was shown to be effective, safe, and easily applicable in men with localized PCa.

Background Accumulating evidence supports that prostate cancer stem-like cells (PCSCs) play significant roles in therapy resistance and metastasis of prostate cancer. Many studies also show that nitric oxide (NO) synthesized by NO synthases can function to promote tumor progression. However, the exact roles of NOSs and NO signaling in the growth regulation of PCSCs and castration-resistant prostate cancer (CRPC) are still not fully understood. Methods The regulatory functions of NOS-NO signaling were evaluated in prostate cancer cells, especially in PCSCs enriched by 3D spheroid culture and CD133/CD44 cell sorting. The molecular mechanisms of NOS-NO signaling in PCSCs growth regulation and tumor metastasis were investigated in PCSCs and mice orthotopic prostate tumor model. Results Endothelial NOS (eNOS) exhibited a significant upregulation in high-grade prostate cancer and metastatic CRPC. Xenograft models of CRPC exhibited notable increased eNOS expression and higher intracellular NO levels. PCSCs isolated from various models displayed significant enhanced eNOS-NO signaling. Functional analyses demonstrated that increased eNOS expression could promote in vivo tumorigenicity and metastatic potential of prostate cancer cells. Characterization of eNOS-NO involved downstream pathway which confirmed that enhanced eNOS signaling could promote the growth of PCSCs and antiandrogen-resistant prostate cancer cells via an activated downstream NO-sGC-cGMP-PKG effector signaling pathway. Interestingly, eNOS expression could be co-targeted by nuclear receptor ERRα and transcription factor ERG in prostate cancer cells and PCSCs. Conclusions Enhanced eNOS-NO signaling could function to promote the growth of PCSCs and also the development of metastatic CRPC. Besides eNOS-NO as potential targets, targeting its upstream regulators (ERRα and ERG) of eNOS-NO signaling could also be the therapeutic strategy for the management of advanced prostate cancer, particularly the aggressive cancer carrying with the TMPRSS2:ERG fusion gene.