Comparison of systematic and combined biopsy for the detection of prostate cancer.

ABSTRACT: Systematic prostate biopsy has limitations, such as overdiagnosis of clinically insignificant prostate cancer and underdiagnosis of clinically significant prostate cancer. Magnetic resonance imaging (MRI)-guided biopsy, a promising alternative, might improve diagnostic accuracy. To compare the cancer detection rates of systematic biopsy and combined biopsy (systematic biopsy plus MRI-targeted biopsy) in Asian men, we conducted a retrospective cohort study of men who underwent either systematic biopsy or combined biopsy at two medical centers (Queen Mary Hospital and Tung Wah Hospital, Hong Kong, China) from July 2015 to December 2022. Descriptive statistics were calculated, and univariate and multivariate logistic regression analyses were performed. The primary and secondary outcomes were prostate cancer and clinically significant prostate cancer. A total of 1391 participants were enrolled. The overall prostate cancer detection rates did not significantly differ between the two groups (36.3% vs 36.6%, odds ratio [OR] = 1.01, 95% confidence interval [CI]: 0.81-1.26, P = 0.92). However, combined biopsy showed a significant advantage in detecting clinically significant prostate cancer (Gleason score ≥ 3+4) in patients with a total serum prostate-specific antigen (tPSA) concentration of 2-10 ng ml-1 (systematic vs combined: 11.9% vs 17.5%, OR = 1.58, 95% CI: 1.08-2.31, P = 0.02). Specifically, in the transperineal biopsy subgroup, combined biopsy significantly outperformed systematic biopsy in the detection of clinically significant prostate cancer (systematic vs combined: 12.6% vs 24.0%, OR = 2.19, 95% CI: 1.21-3.97, P = 0.01). These findings suggest that in patients with a tPSA concentration of 2-10 ng ml-1, MRI-targeted biopsy may be of greater predictive value than systematic biopsy in the detection of clinically significant prostate cancer.

The Impact of Prostate-Specific Antigen Screening on Prostate Cancer Incidence and Mortality in China: 13-Year Prospective Population-Based Cohort Study.

BACKGROUND: The status of prostate-specific antigen (PSA) screening is unclear in China. Evidence regarding the optimal frequency and interval of serial screening for prostate cancer (PCa) is disputable. OBJECTIVE: This study aimed to depict the status of PSA screening and to explore the optimal screening frequency for PCa in China. METHODS: A 13-year prospective cohort study was conducted using the Chinese Electronic Health Records Research in Yinzhou study's data set. A total of 420,941 male participants aged ≥45 years were included between January 2009 and June 2022. Diagnosis of PCa, cancer-specific death, and all-cause death were obtained from the electronic health records and vital statistic system. Hazard ratios (HRs) with 95% CIs were estimated using Cox regression analysis. RESULTS: The cumulative rate of ever PSA testing was 17.9% with an average annual percent change (AAPC) of 8.7% (95% CI 3.6%-14.0%) in the past decade in China. People with an older age, a higher BMI, higher waist circumference, tobacco smoking and alcohol drinking behaviors, higher level of physical activity, medication use, and comorbidities were more likely to receive PSA screening, whereas those with a lower education level and a widowed status were less likely to receive the test. People receiving serial screening ≥3 times were at a 67% higher risk of PCa detection (HR 1.67; 95% CI 1.48-1.88) but a 64% lower risk of PCa-specific mortality (HR 0.36; 95% CI 0.18-0.70) and a 28% lower risk of overall mortality (HR 0.72; 95% CI 0.67-0.77). People following a serial screening strategy at least once every 4 years were at a 25% higher risk of PCa detection (HR 1.25; 95% CI 1.13-1.36) but 70% (HR 0.30; 95% CI 0.16-0.57) and 23% (HR 0.77; 95% CI 0.73-0.82) lower risks of PCa-specific and all-cause mortality, respectively. CONCLUSIONS: This study reveals a low coverage of PSA screening in China and provides the first evidence of its benefits in the general Chinese population. The findings of this study indicate that receiving serial screening at least once every 4 years is beneficial for overall and PCa-specific survival. Further studies based on a nationwide population and with long-term follow-up are warranted to identify the optimal screening interval in China.

Risk of second primary cancers after a diagnosis of first primary cancer: A pan-cancer analysis and Mendelian randomization study.

Background: The risk of second primary cancers (SPC) is increasing after the first primary cancers (FPC) are diagnosed and treated. The underlying causal relationship remains unclear. Methods: We conducted a pan-cancer association (26 cancers) study in the Surveillance, Epidemiology, and End Results (SEER) database (non-Hispanic whites). The standardized incidence ratio (SIR) was estimated as the risk of SPCs in cancer survivors based on the incidence in the general population. Furthermore, the causal effect was evaluated by two-sample Mendelian Randomization (MR, 13 FPCs) in the UK Biobank (UKB, n=459,136,, European whites) and robust analysis (radial MR and Causal Analysis Using Summary Effect estimates, CAUSE). Results: We found 11 significant cross-correlations among different cancers after harmonizing SIR and MR results. Whereas only 4 of them were confirmed by MR to have a robust causal relationship. In particular, patients initially diagnosed with oral pharyngeal cancer would have an increased risk of non-Hodgkin lymphoma (SIRSEER = 1.18, 95%Confidence Interval [CI]:1.05-1.31, ORradial-MR=1.21, 95% CI:1.13-1.30, p=6.00 × 10-3; ORcause = 1.17, 95% CI:1.05-1.31, p=8.90 × 10-3). Meanwhile, ovary cancer was identified to be a risk factor for soft tissue cancer (SIRSEER = 1.72, 95%Confidence Interval [CI]:1.08-2.60, ORradial-MR=1.39, 95% CI:1.22-1.58, p=1.07 × 10-3; ORcause = 1.36, 95% CI:1.16-1.58, p=0.01). And kidney cancer was likely to cause the development of lung cancer (SIRSEER = 1.28, 95%Confidence Interval [CI]:1.22-1.35, ORradial-MR=1.17, 95% CI:1.08-1.27, p=6.60 × 10-3; ORcause = 1.16, 95% CI:1.02-1.31, p=0.05) and myeloma (SIRSEER = 1.54, 95%Confidence Interval [CI]:1.33-1.78, ORradial-MR=1.72, 95% CI:1.21-2.45, p=0.02; ORcause = 1.49, 95% CI:1.04-2.34, p=0.02). Conclusions: A certain type of primary cancer may cause another second primary cancer, and the profound mechanisms need to be studied in the future. Funding: This work was in supported by grants from National Natural Science Foundation of China (Grant No. 81972645), Innovative research team of high-level local universities in Shanghai, Shanghai Youth Talent Support Program, intramural grant of The University of Hong Kong to Dr. Rong Na, and Shanghai Sailing Program (22YF1440500) to Dr. Da Huang.

Better cancer treatment and early detection have increased survival rates among patients with cancer. But some cancer survivors can develop a second cancer called a second primary cancer. Second primary cancers may occur months or years after successful treatment of the primary cancer. They are not caused by the spread of the original tumor like a cancer metastasis. Instead, they appear to occur independently in another location or tissue. Scientists are trying to understand what causes second primary cancers. Genetics, lifestyle, the environment, treatments used for the initial tumor, or other factors may all contribute to individuals developing a second cancer. Learning more about who is at risk of developing a second cancer and why, may lead to new prevention, treatment or screening strategies. Ruan, Huang et al. found that people with some primary cancers have an increased risk of secondary primary cancers in specific tissues. The researchers first looked at the Surveillance, Epidemiology, and End Results (SEER) database that tracks US cancer patients to see if different types of cancers were more likely to lead to a second primary cancer. Then, the team conducted a comprehensive analysis for a causal relationship in a second extensive health database, the UK Biobank, to determine if the primary cancers may have caused the second primary cancer. The study showed that patients diagnosed with mouth or throat cancers were at increased risk of later developing a lymph node cancer called non-Hodgkin lymphoma. Patients diagnosed with ovarian cancer were at increased risk of later developing cancer in one of the body's soft tissues. Kidney cancer is likely the cause of later lung cancers and a type of blood cancer called myeloma. Understanding the relationships between an initial and later cancer diagnosis is essential to improve cancer survivors' care. It is especially important for patients diagnosed early in life. More studies are needed to confirm the links Ruan, Huang et al. identified and to understand the mechanism. If more studies confirm the associations, physicians may want to screen survivors for specific cancers. Scientists may also be able to use the information to develop new strategies to help prevent or treat secondary primary cancers.

Prostate health index can stratify patients with Prostate Imaging Reporting and Data System score 3 lesions on magnetic resonance imaging to reduce prostate biopsies.

We aim to evaluate prostate health index as an additional risk-stratification tool in patients with Prostate Imaging Reporting and Data System score 3 lesions on multiparametric magnetic resonance imaging. Men with biochemical or clinical suspicion of having prostate cancer who underwent multiparametric magnetic resonance imaging in two tertiary centers (Queen Mary Hospital and Princess Margaret Hospital, Hong Kong, China) between January 2017 and June 2022 were included. Ultrasound-magnetic resonance imaging fusion biopsies were performed after prostate health index testing. Those who only had Prostate Imaging Reporting and Data System score 3 lesions were further stratified into four prostate health index risk groups and the cancer detection rates were analyzed. Out of the 747 patients, 47.3% had Prostate Imaging Reporting and Data System score 3 lesions only. The detection rate of clinically significant prostate cancer in this group was 15.0%. The cancer detection rates of clinically significant prostate cancer had statistically significant differences: 5.3% in prostate health index <25.0, 7.4% in prostate health index 25.0-34.9, 17.9% in prostate health index 35.0-54.9, and 52.6% in prostate health index ≥55.0 (P < 0.01). Among the patients, 26.9% could have avoided a biopsy with a prostate health index <25.0, at the expense of a 5.3% risk of missing clinically significant prostate cancer. Prostate health index could be used as an additional risk stratification tool for patients with Prostate Imaging Reporting and Data System score 3 lesions. Biopsies could be avoided in patients with low prostate health index, with a small risk of missing clinically significant prostate cancer.

Genetic Polymorphisms of the Telomerase Reverse Transcriptase Gene in Relation to Prostate Tumorigenesis, Aggressiveness and Mortality: A Cross-Ancestry Analysis.

BACKGROUND: Telomerase reverse transcriptase (TERT) has been consistently associated with prostate cancer (PCa) risk. However, few studies have explored the association between TERT variants and PCa aggressiveness. METHODS: Individual and genetic data were obtained from UK Biobank and a Chinese PCa cohort (Chinese Consortium for Prostate Cancer Genetics). RESULTS: A total of 209,694 Europeans (14,550 PCa cases/195,144 controls) and 8873 Chinese (4438 cases/4435 controls) were involved. Nineteen susceptibility loci with five novel ones (rs144704378, rs35311994, rs34194491, rs144020096, and rs7710703) were detected in Europeans, whereas seven loci with two novel ones (rs7710703 and rs11291391) were discovered in the Chinese cohort. The index SNP for the two ancestries was rs2242652 (odds ratio [OR] = 1.16, 95% confidence interval [CI]:1.12-1.20, p = 4.12 × 10-16) and rs11291391 (OR = 1.73, 95%CI:1.34-2.25, p = 3.04 × 10-5), respectively. SNPs rs2736100 (OR = 1.49, 95%CI:1.31-1.71, p = 2.91 × 10-9) and rs2853677 (OR = 1.74, 95%CI:1.52-1.98, p = 3.52 × 10-16) were found significantly associated with aggressive PCa, while rs35812074 was marginally related to PCa death (hazard ratio [HR] = 1.61, 95%CI:1.04-2.49, p = 0.034). Gene-based analysis showed a significant association of TERT with PCa (European: p = 3.66 × 10-15, Chinese: p = 0.043) and PCa severity (p = 0.006) but not with PCa death (p = 0.171). CONCLUSION: TERT polymorphisms were associated with prostate tumorigenesis and severity, and the genetic architectures of PCa susceptibility loci were heterogeneous among distinct ancestries.

Causal Effects of Modifiable Behaviors on Prostate Cancer in Europeans and East Asians: A Comprehensive Mendelian Randomization Study.

OBJECTIVE: Early evidence is disputable for the effects of modifiable lifestyle behaviors on prostate cancer (PCa) risk. No research has yet appraised such causality in different ancestries using a Mendelian randomization (MR) approach. METHODS: A two-sample univariable and multivariable MR analysis was performed. Genetic instruments associated with lifestyle behaviors were selected based on genome-wide association studies. Summary-level data for PCa were obtained from PRACTICAL and GAME-ON/ELLIPSE consortia for Europeans (79,148 PCa cases and 61,106 controls), and ChinaPCa consortium for East Asians (3343 cases and 3315 controls). Replication was performed using FinnGen (6311 cases and 88,902 controls) and BioBank Japan data (5408 cases and 103,939 controls). RESULTS: Tobacco smoking was identified as increasing PCa risks in Europeans (odds ratio [OR]: 1.95, 95% confidence interval [CI]: 1.09-3.50, p = 0.027 per standard deviation increase in the lifetime smoking index). For East Asians, alcohol drinking (OR: 1.05, 95%CI: 1.01-1.09, p = 0.011) and delayed sexual initiation (OR: 1.04, 95%CI: 1.00-1.08, p = 0.029) were identified as risk factors, while cooked vegetable consumption (OR: 0.92, 95%CI: 0.88-0.96, p = 0.001) was a protective factor for PCa. CONCLUSIONS: Our findings broaden the evidence base for the spectrum of PCa risk factors in different ethnicities, and provide insights into behavioral interventions for prostate cancer.

Molecular characteristics of Asian male BRCA-related cancers.

PURPOSE: Germline mutations of BRCA1 or BRCA2 predispose men to develop various cancers, including breast cancers and prostate cancers. Male breast cancer (MBC) is a rare disease while prostate cancer (PRC) is uncommon in young men at the age of less than 40. The prevalence of BRCA genes in Asian male patients has to be elevated. METHODS: Germline mutations screening was performed in 98 high-risk Chinese MBC and PRC patients. RESULT: We have identified 16 pathogenic BRCA2 mutation carriers, 12 were MBC patients, 2 were PRC patients and 2 were patients with both MBC and PRC. The mutation percentages were 18.8%, 6.7% and 50% for MBC, PRC and both MBC and PRC patients, respectively. BRCA2 gene mutations confer a significantly higher risk of breast/prostate cancers in men than those with BRCA1 mutations. BRCA mutated MBC patients had a younger age of diagnosis and strong family histories of breast cancers while BRCA mutated PRC patients had strong family histories of ovarian cancers. CONCLUSION: Male BRCA carriers with breast cancers or prostate cancers showed distinct clinical and molecular characteristics, a male-specific genetic screening model would be useful to identify male cancer patients who have a high risk of BRCA mutation.

CRISPR screening reveals gleason score and castration resistance related oncodriver ring finger protein 19 A (RNF19A) in prostate cancer.

Prostate cancer (PCa) is one of the most lethal causes of cancer-related death in male. It is characterized by chromosomal instability and disturbed signaling transduction. E3 ubiquitin ligases are well-recognized as mediators leading to genomic alterations and malignant phenotypes. There is a lack of systematic study on novel oncodrivers with genomic and clinical significance in PCa. In this study we used clustered regularly interspaced short palindromic repeats (CRISPR) system to screen 656 E3 ubiquitin ligases as oncodrivers or tumor repressors in PCa cells. We identified 51 significantly changed genes, and conducted genomic and clinical analysis on these genes. It was found that the Ring Finger Protein 19 A (RNF19A) was a novel oncodriver in PCa. RNF19A was frequently amplified and highly expressed in PCa and other cancer types. Clinically, higher RNF19A expression correlated with advanced Gleason Score and predicted castration resistance. Mechanistically, transcriptomics, quantitative and ubiquitination proteomic analysis showed that RNF19A ubiquitylated Thyroid Hormone Receptor Interactor 13 (TRIP13) and was transcriptionally activated by androgen receptor (AR) and Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A). This study uncovers the genomic and clinical significance of a oncodriver RNF19A in PCa. The results of this study indicate that targeting AR/HIF1A-RNF19A-TRIP13 signaling axis could be an alternative option for PCa diagnosis and therapy.

Outcomes of radical prostatectomy in a 20-year localized prostate cancer single institution series in China.

The long-term survival outcomes of radical prostatectomy (RP) in Chinese prostate cancer (PCa) patients are poorly understood. We conducted a single-center, retrospective analysis of patients undergoing RP to study the prognostic value of pathological and surgical information. From April 1998 to February 2022, 782 patients undergoing RP at Queen Mary Hospital of The University of Hong Kong (Hong Kong, China) were included in our study. Multivariable Cox regression analysis and Kaplan-Meier analysis with stratification were performed. The 5-year, 10-year, and 15-year overall survival (OS) rates were 96.6%, 86.8%, and 70.6%, respectively, while the 5-year, 10-year, and 15-year PCa-specific survival (PSS) rates were 99.7%, 98.6%, and 97.8%, respectively. Surgical International Society of Urological Pathology PCa grades (ISUP Grade Group) ≥4 was significantly associated with poorer PSS (hazard ratio [HR] = 8.52, 95% confidence interval [CI]: 1.42-51.25, P = 0.02). Pathological T3 stage was not significantly associated with PSS or OS in our cohort. Lymph node invasion and extracapsular extension might be associated with worse PSS (HR = 20.30, 95% CI: 1.22-336.38, P = 0.04; and HR = 7.29, 95% CI: 1.22-43.64, P = 0.03, respectively). Different surgical approaches (open, laparoscopic, or robotic-assisted) had similar outcomes in terms of PSS and OS. In conclusion, we report the longest timespan follow-up of Chinese PCa patients after RP with different approaches.

The diagnostic value of rapid urine test platform UF-5000 for suspected urinary tract infection at the emergency department.

Background and objective: Urine culture is time consuming, which may take days to get the results and impede further timely treatment. Our objective is to evaluate whether the fast urinalysis and bacterial discrimination system called Sysmex UF-5000 may predict urinary tract infections (UTIs) (within minutes) compared with the clinical routine test in suspected UTI patients. In addition, we aimed to explore the accuracy of microbiologic information by UF-5000. Materials and Methods: Consecutive patients who were admitted from the emergency department at Queen Mary Hospital (a tertiary hospital in Hong Kong) from June 2019 to February 2020 were enrolled in the present study. The dipstick test, manual microscopic test with culture, and Sysmex UF-5000 test were performed in the urine samples at admission. Results: A total of 383 patients were finally included in the present study. UF-5000 urinalysis (area under the receiver operator characteristic curve, AUC=0.821, confidence interval, 95%CI: 0.767-0.874) outperformed the dipstick test (AUC=0.602, 95%CI: 0.550-0.654, P=1.32×10-10) for predicting UTIs in patients without prior antibiotic treatment. A significant net benefit from UF-5000 was observed compared with the dipstick test (NRI=39.9%, 95%CI: 19.4-60.4, P=1.36 × 10-4). The urine leukocyte tested by UF-5000 had similar performance (AUC) for predicting UTI compared with the manual microscopic test (P=0.27). In patients without a prior use of antibiotics, the concordance rates between UF-5000 and culture for predicting Gram-positive or -negative bacteriuria and a negative culture were 44.7% and 96.2%, respectively. Conclusions: UF-5000 urinalysis had a significantly better predictive value than the dipstick urine test for predicting UTIs.

Host and viral determinants for efficient SARS-CoV-2 infection of the human lung.

Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs.

SARS-CoV-2 Induces a More Robust Innate Immune Response and Replicates Less Efficiently Than SARS-CoV in the Human Intestines: An Ex Vivo Study With Implications on Pathogenesis of COVID-19.

BACKGROUND AND AIMS: Besides prominent respiratory involvement, gastrointestinal manifestations are commonly reported in Coronavirus Disease 2019 (COVID-19) patients. We compared infection of ex vivo human intestinal tissues by SARS-CoV-2 and SARS-CoV with respect to their replication kinetics and immune activation profile. METHODS: Human intestinal tissues were obtained from patients while undergoing surgical operations at Queen Mary Hospital, Hong Kong. Upon surgical removal, the tissues were immediately processed and infected with SARS-CoV-2 or SARS-CoV. Replication kinetics were determined with immunohistochemistry, qRT-PCR, and plaque assays. Immune activation in the infected intestinal tissues was assessed by detecting the gene expression of interferons and representative pro-inflammatory cytokines and chemokines. RESULTS: SARS-CoV-2 could infect and productively replicate in the ex vivo human intestinal tissues with release of infectious virus particles, but not in ex vivo human liver and kidney tissues. Importantly, SARS-CoV-2 replicated less efficiently than SARS-CoV, induced less cytopathology in the human intestinal epithelium, and induced a more robust innate immune response including the activation of both type I and type III interferons, than SARS-CoV in human intestinal tissues. CONCLUSION: Using the ex vivo human intestinal tissues as a physiologically relevant model, our data indicated that SARS-CoV-2 could productively replicate in the human gut and suggested that the gastrointestinal tract might serve as an alternative route of virus dissemination. SARS-CoV-2 replicated less efficiently and induced less cytopathology than SARS-CoV in keeping with the clinical observations reported for COVID-19 and SARS, which might be the result of a more robust immune activation by SARS-CoV-2 than SARS-CoV in the human intestine.

Anterior perineal hernia after anterior exenteration.

Perineal hernia is a rare complication of anterior exenteration. We reported this complication after an anterior exenteration for bladder cancer with bleeding complication requiring packing and second-look laparotomy. Perineal approach is a simple and effective method for repair of perineal hernia.

Trocar-site hernia at the 8-mm robotic port after robot-assisted laparoscopic prostatectomy: a case report and review of the literature.

Trocar-site hernia is an uncommon but serious complication after laparoscopic surgery as it frequently requires surgical intervention. We describe a 75-year-old man with Gleason score 4 + 3, clinical stage T1c prostate adenocarcinoma who underwent an uneventful robot-assisted transperitoneal laparoscopic radical prostatectomy. On post-operative day four, he developed symptoms of small bowel obstruction due to herniation and incarceration of the small bowels in a Spigelian-type hernia at the left lower quadrant 8-mm trocar site. Surgical exploration was performed via a mini-laparotomy to reduce the bowel and repair the fascial layers. A literature search was performed to review other cases of trocar-site hernia through the 8-mm robotic port after robot-assisted surgery and the suggested methods of prevention.