Causal relationship between folic acid and prostate cancer risk: Insights from Mendelian randomization analysis.

OBJECTIVE: Folic acid is a commonly used dietary supplement of trace element, but it may increase the risk of prostate cancer (PCa). The aim of this study was to investigate the causal relationship between PCa and folic acid supplementation, as well as dietary folate equivalents, using Mendelian randomization (MR) analysis. METHODS: The Genome-Wide Association Study (GWAS) data of folic acid supplementation and dietary folate equivalents were selected from UK Biobank. Meta-analysis of GWASs of PCa was obtained from PCa Association Group to Investigate Cancer-Associated Alterations in the Genome consortium. MR analysis was performed with inverse variance weighted (IVW) method, MR-Egger regression, simple mode, weighted median, and weighted mode analysis. Heterogeneity and horizontal pleiotropy tests and reverse MR analysis were conducted to assess the robustness and reliability of the causal inference. RESULTS: Six single nucleotide polymorphisms (SNPs) associated with folic acid supplementation and five SNPs associated with dietary folate equivalents were identified as instrumental variables. Genetically predicted folic acid supplementation was associated with an increased risk of PCa (OR 1.200, p < 0.001, by IVW method), and there was no evidence of heterogeneity, horizontal pleiotropy, or significant reverse causality (all p > 0.05). In contrast, dietary folate equivalents showed no significant correlation with PCa (p > 0.05 for all five MR methods). CONCLUSION: This study demonstrated an association between increased risk of PCa and folic acid supplementation, but not with dietary folate equivalents. These findings have implications for public health interventions and personalized preventive strategies for PCa.

CXCL5 is a potential diagnostic and prognostic marker for bladder cancer patients.

Chemokine C-X-C motif ligand 5 (CXCL5) is critical for bladder cancer growth and progression. Our previous study demonstrated that increase of CXCL5 in bladder cancer cell lines had an effect on tumor growth and progression. This study aims to investigate the expression of CXCL5 in tissue and urine of bladder cancer patients, in relation to clinicopathologic parameters, and as a predictive value in diagnosing and evaluating bladder cancer. Urothelial bladder cancer tissues from 255 patients were profiled for CXCL5 alterations by immunohistochemistry. Urine samples collected from patients with bladder cancer and urinary tract infections as well as healthy volunteers were analyzed by ELISA. High expression of CXCL5 in bladder cancer tissue was correlated with TNM stage (P = 0.012), cancer grade (P = 0.001), and lymph node metastasis (P = 0.007). CXCL5 alterations were associated with overall survival (P = 0.007), progression free survival (P = 0.004), and recurrence free survival in muscle invasive bladder cancers (P = 0.026). CXCL5 expression in the urine of bladder cancer patients was significantly different from urinary tract infection patients (P = 0.001) and healthy volunteers. However, urine leukocytes may predict CXCL5 levels (ß = 0.56, P < 0.001, R (2) = 0.314). CXCL5 expression in urine was also related to bladder cancer TNM stage (P = 0.039), lymph node metastasis (P = 0.023), tumor size (P = 0.007), and tumor grade (P = 0.005). The sensitivity and specificity for CXCL5/creatinine in predicting bladder cancer were 80.4 and 61.3 %, respectively. These results suggest increased CXCL5 expression in cancer tissue predicts poor survival in bladder cancer patients. CXCL5 expression in urine is useful in a minimally invasive modality for bladder cancer diagnosis. However, urine leukocytes are significant predictors of CXCL5 levels and may affect its result in bladder cancer diagnosis.

Real-world progression in the survival of de novo Metastatic prostate cancer over the past decade.

BACKGROUND: The impact of evolving treatment strategies for metastatic prostate cancer (mPCa) on real-world survival is not well understood. We analyzed changes in mPCa survival over the past decade and discussed the potential driving factors behind these changes. METHODS: Our study involved 43,228 mPCa patients (2004-2020) from the SEER database, divided into 4 diagnostic periods. We used a multivariate Cox proportional hazards model to evaluate diagnostic periods' influence on overall mortality (OM) and prostate cancer-specific mortality (PSM), and calculated relative median survival improvements between adjacent periods. Subgroup analyses based on age and distant metastasis sites were conducted. RESULTS: Patients diagnosed in 2016 to 2020 experienced significantly reduced mortality risk compared to those in 2004 to 2007 (HR 0.64 for OM, HR 0.62 for CSM, both P < 0.001). The study period witnessed an absolute improvement in median overall survival (OS) and prostate cancer-specific survival (PCSS), 17 months (54.8%) and 25 months (67.6%) respectively. The most rapid relative survival improvement occurred post-2016, with a 29.7% increase in median OS and a 37.8% increase in PCSS compared to 2012 to 2015. There was a significant reduction in mortality risk throughout the study period in both age groups (age <75 and ≥75), but absolute survival gains were smaller in the older group (24 months [68.6%] vs. 8 months [32%] for OS, 36 months [90.0%] vs. 11 months [33.3%] for PCSS), with lower relative survival improvements after 2016 (37.2% vs. 17.9% for OS, 49% vs. 22.2% for PCSS). All metastasis site subgroups (except M1a) exhibited a significant reduction in mortality risk (all P < 0.001). Absolute survival improvements were 58 months (134.9%) for M1a, 16 months (50.0%) for M1b, and 17 months (54.8%) for M1c. CONCLUSION: The survival of mPCa have significantly improved over the past decade, although the progress is slower in elderly patients. Investigating the underlying reasons for survival differences among various patient profiles can further refine mPCa treatment strategies.

Clinicopathological characteristics, surgical treatments, and oncological outcomes of localized primary unifocal urothelial carcinoma involving the ureterovesical junction.

OBJECTIVE: To investigate clinicopathological characteristics, surgical treatments, and oncological outcomes of patients with localized primary unifocal urothelial carcinoma involving the ureterovesical junction (UC-UVJ). PATIENTS AND METHODS: Localized primary unifocal UC-UVJ cases in patients admitted to our hospital from March 2013 to August 2021 were reviewed. Clinicopathological parameters, perioperative data, and oncological outcomes were compared between patients grouped by tumor location and surgical treatment. RESULTS: A total of 130 patients with localized primary unifocal UC-UVJ were enrolled in this study. These included 72 cases of bladder cancer (BC) involving the ureteral orifice, and 58 cases of upper urinary tract urothelial carcinoma (UTUC) involving the intramural ureter. The proportion of male patients, hydronephrosis, flank pain/abdominal pain, and tumor size differed significantly between the BC and UTUC groups (all P < 0.05). During the median follow-up period of 32.9 months, 49 cases (37.7%) recurred and 29 (22.3%) died from urothelial carcinoma (UC), though no statistical difference in recurrence (P = 0.436) or cancer-specific mortality (P = 0.653) was observed between the BC and UTUC groups. Cox proportional hazards regression analysis identified age, tumor grade, and lymphovascular invasion (LVI) as independent predictors of cancer-specific survival (CSS), and sex, T stage, tumor grade, and LVI as independent predictors of recurrence-free survival (RFS). CONCLUSION: Owing to positional properties, patients with localized primary unifocal UC-UVJ exhibited significant heterogeneity, leading to varied treatment strategies. No statistically significant differences in CSS or RFS were observed between the BC and UTUC groups. Furthermore, age, sex, T stage, tumor grade, and LVI should be carefully considered in clinical practice because of their associations with CSS and RFS.

Prognostic impact of tumor size in ureteral cancer following segmental ureterectomy.

OBJECTIVE: To evaluate the classification and prognostic effects of a 2 cm tumor size in patients with ureteral cancer (UC) undergoing segmental ureterectomy (SU). PATIENTS AND METHODS: A total of 75 patients with UC who underwent SU in our hospital between April 2013 and April 2023 were included in this study. The study population was grouped based on tumor size, which was defined as the maximum diameter of the pathological specimens, resulting in 30 patients (40.0%) with tumor size <2 cm and 45 patients (60.0%) with tumor size ≥2 cm. The clinicopathological variables, perioperative parameters, and oncological outcomes were compared between the 2 groups. The endpoints were recurrence-free survival (RFS), and cancer-specific survival (CSS). RESULTS: A tumor ≥2 cm was related to a higher positive rate of urine exfoliative cytology (P = 0.049) and fewer preoperative ureteroscopies (P = 0.033) than tumors <2 cm. After a follow-up of 6.3 to 128.7 months (median 40.2 months), 23 cases (30.7%) experienced recurrence and 11 patients (14.7%) succumbed to UC in the end. Compared to those with tumor size <2 cm, patients with tumor size ≥2 cm experienced more urothelial recurrence (P = 0.032). Kaplan-Meier analysis demonstrated that patients with tumor size ≥2 cm displayed inferior urothelial RFS than those with tumor size <2 cm (P = 0.026). Multivariate Cox analysis identified tumor size ≥2 cm, and pathological stage ≥T2 were significant prognostic factors of poor urothelial RFS (all P < 0.05). CONCLUSION: Tumor size ≥2 cm was associated with a high rate of urothelial recurrence and served as an independent prognostic factor of adverse urothelial RFS in SU-treated patients with UC. Patients are advised to select surgical treatments for UC following the EAU guidelines.

Integrated analysis of mRNA-single nucleotide polymorphism-microRNA interaction network to identify biomarkers associated with prostate cancer.

Background: Prostate cancer is one of the most common malignancies among men worldwide currently. However, specific mechanisms of prostate cancer were still not fully understood due to lack of integrated molecular analyses. We performed this study to establish an mRNA-single nucleotide polymorphism (SNP)-microRNA (miRNA) interaction network by comprehensive bioinformatics analysis, and search for novel biomarkers for prostate cancer. Materials and methods: mRNA, miRNA, and SNP data were acquired from Gene Expression Omnibus (GEO) database. Differential expression analysis was performed to identify differentially expressed genes (DEGs) and miRNAs (DEMs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, protein-protein interaction (PPI) analysis and expression quantitative trait loci (eQTL) analysis of DEGs were conducted. SNPs related to DEMs (miRSNPs) were downloaded from the open-source website MirSNP and PolymiRTS 3.0. TargetScan and miRDB databases were used for the target mRNA prediction of miRNA. The mRNA-SNP-miRNA interaction network was then constructed and visualized by Cytoscape 3.9.0. Selected key biomarkers were further validated using the Cancer Genome Atlas (TCGA) database. A nomogram model was constructed to predict the risk of prostate cancer. Results: In our study, 266 DEGs and 11 DEMs were identified. KEGG pathway analysis showed that DEGs were strikingly enriched in focal adhesion and PI3K-Akt signaling pathway. A total of 60 mRNA-SNP-miRNAs trios were identified to establish the mRNA-SNP-miRNA interaction network. Seven mRNAs in mRNA-SNP-miRNA network were consistent with the predicted target mRNAs of miRNA. These results were largely validated by the TCGA database analysis. A nomogram was constructed that contained four variables (ITGB8, hsa-miR-21, hsa-miR-30b and prostate-specific antigen (PSA) value) for predicting the risk of prostate cancer. Conclusion: Our study established the mRNA-SNP-miRNA interaction network in prostate cancer. The interaction network showed that hsa-miR-21, hsa-miR-30b, and ITGB8 may be utilized as new biomarkers for prostate cancer.

Percutaneous Microcoil Localization of a Small, Totally Endophytic Renal Mass for Nephron-Sparing Surgery: A Case Report and Literature Review.

Small, totally endophytic renal masses present a technical challenge for surgical extirpation due to poor identifiability during surgery. The method for the precise localization of totally endophytic tumours before nephron-sparing surgery could be optimized. An asymptomatic 70-year-old male presented with a right-sided, 16-mm, totally endophytic renal mass on computed tomography (CT). CT-guided percutaneous microcoil localization was carried out prior to laparoscopy to provide a direction for partial nephrectomy. During the 25 minutes of the localization procedure, the patient underwent five local CT scans, and his cumulative effective radiation dosage was 5.1 mSv. The span between localization and the start of the operation was 15 hours. The laparoscopic operation time was 105 minutes, and the ischaemia time was 25 minutes. The postoperative recovery was smooth, and no perioperative complications occurred. Pathology showed the mass to be renal clear cell carcinoma, WHO/ISUP grade 2, with a 2-mm, clear surgical margin. The patient remained free of recurrence on follow-up for eleven months. To our knowledge, this application of microcoil implantation prior to laparoscopic partial nephrectomy towards an intrarenal mass could be an early reported attempt for the localized method applied in renal surgery. The percutaneous microcoil localization of endophytic renal tumours is potentially safe and effective prior to laparoscopic partial nephrectomy.

ZSCAN16 promotes proliferation, migration and invasion of bladder cancer via regulating NF-kB, AKT, mTOR, P38 and other genes.

BACKGROUND: As one of the most common genitourinary malignancies worldwide, bladder cancer affects about 3.4 million people globally, with 430,000 new cases a year since 2015. Despite the advances in bladder cancer diagnosis and therapy, there has been little progress in the patients' overall survival in nearly 30 years. Therefore, investigating novel molecular therapeutic targets is required to gain insight into the tumorigenesis of bladder cancer, which ultimately may be used to develop more effective therapeutic strategies. METHODS: Herein, we used gene knockdown in vitro and in vivo to unveil the unknown roles of ZSCAN16 in bladder cancer. Afterward, to decipher the unknown regulatory role of ZSCAN16 in tumor progression, we verified that a bunch of genes including NF-κB, AKT, mTOR, and P38 were the key downstream regulators of ZSCAN16 by western blot and rescue experiments. RESULTS: We found high expression of ZSCAN16 transcripts in bladder cancer cells and tumor samples from the TCGA database and tissue microarray bank, demonstrated in correlation with poor prognosis for bladder cancer patients. The in vitro experiments indicated that the silencing of ZSCAN16 by shRNA lentivirus promoted apoptosis and inhibited proliferation, colony formation, as well as migration and invasion in T24 cells. By investigating the signaling pathways, we proved ZSCAN16 play a novel role as oncogenic gene in bladder cancer by regulating NF-κB, AKT, mTOR, P38 and other genes. Furthermore, the in vivo experiments identified that ZSCAN16 knockdown retarded the tumor growth in nude mice. CONCLUSIONS: In summary, these findings revealed that ZSCAN16 is a potential novel oncogene in the development and progression of bladder cancer. This study will shed light on developing novel therapeutic targets in the future treatment of bladder cancer.

Treatment of upper urinary tract stones with flexible ureteroscopy in children.

INTRODUCTION: This single-centre, retrospective study aimed to assess the efficacy and safety of flexible ureteroscopy (FURS) combined with holmium laser lithotripsy in treating children with upper urinary tract stones. METHODS: From June 2014 to October 2015, a total of 100 children (74 boys and 26 girls) with upper urinary tract stones were treated using FURS. A 4.7 Fr double-J stent was placed two weeks before operation. Patients were considered stone-free when the absence of residual fragments was observed on imaging studies. The preoperative, operative, and postoperative data of the patients were retrospectively analyzed. RESULTS: A total of 100 pediatric patients with a mean age of 3.51±1.82 years underwent 131 FURS and holmium laser lithotripsy. Mean stone diameter was 1.49±0.92 cm. Average operation time was 30.8 minutes (range 15-60). The laser power was controlled between 18 and 32 W, and the energy maintained between 0.6 and 0.8 J at any time; laser frequency was controlled between 30 and 40 Hz. Complications were observed in 69 (69.0 %) patients and classified according to the Clavien system. Postoperative hematuria (Clavien I) occurred in 64 (64.0 %) patients. Postoperative urinary tract infection with fever (Clavien II) was observed in 8/113 (7.1%) patients. No ureteral perforation and mucosa avulsion occurred. The overall stone-free rate of single operation was 89/100 (89%). Stone diameter and staghorn calculi were significantly associated with stone-free rate. CONCLUSIONS: FURS and holmium laser lithotripsy is effective and safe in treating children with upper urinary tract stones.

[Carcinoma recurrence rates after laparoscopic nephroureterectomy in patients undergoing transurethral incision of the ureteral orifice and open excision of bladder cuff].

OBJECTIVE: To compare the oncologic efficacy of transurethral incision of the ureteral orifice and open excision of bladder cuff in retroperitoneal laparoscopic nephroureterectomy (LNU) for patients with upper tract urothelium carcinoma. METHODS: The hospital records of 86 patients with upper tract urothelium carcinoma who underwent laparoscopic nephroureterectomy were reviewed retrospectively. 53 of the 86 patients, 22 males and 31 females, aged (68.6+/-14.1), underwent transurethral incision of the ureteral orifice (TUIUO), and 33, 14 males and 19 females, aged (72.4+/-15.2), underwent open excision of bladder cuff. Electric cauterization of the ureteral orifice was performed prior to resection. Follow-up was conducted for 28 (3-47) months. RESULTS: In all the specimens in the TUIUO group scar at the ureter orifice caused by electric excision could be seen. Test to check the pressure of distal ureter in 25 specimens proved that the ureters were all sealed. The distal ureter end began to leak at the water pressure of 135 cm in 1 case, at the water pressure of 167 cm in 1 case, and at 175 cm in 2 cases, but no leaking was seen even at 197 cm H2O in the other cases. Recurrence of bladder tumor was seen in 13 of the 53 patients of the TUIUO group and in 8 of the 33 patients of the open excision of bladder cuff group. Local recurrence developed in one case with the tumor at stage pT4N0M0 8 months after operation. CONCLUSION: Electric cauterization of the ureteral orifice prior to resection effectively ensures the leakproofness of the distal ureter end during LNU. As compared with open excision of bladder cuff, TUIUO does not increase the rate of neoplasm recurrence.

Association between PSCA mRNA expression levels and rs2294008 polymorphism in transitional cell cancer of the bladder.

Prostate stem cell antigen (PSCA) was originally identified as a gene that is overexpressed in prostate cancer, and correlates with prostate cancer progression and prognosis. Recently, a significant association has been identified between the PSCA rs2294008 (C>T) polymorphism and the risk of developing bladder cancer. Therefore, the present study investigated the different expression levels of PSCA mRNA in transitional cell carcinoma (TCC) of the bladder and normal bladder tissue. Furthermore, the association between PSCA mRNA expression levels in TCC and different rs2294008 (C>T) genotypes and various clinicopathological features, including tumor stage and grade, were evaluated. Reverse transcription-quantitative polymerase chain reaction was performed on 80 TCC samples and 38 samples of normal bladder urothelium from TCC patients who underwent transurethral resection of bladder tumor or radical cystectomy at the Beijing Friendship Hospital (Beijing, China) between September 2010 and May 2011. Genomic DNA was extracted from tumor tissue and sequenced to determine the rs2294008 (C>T) genotype. PSCA mRNA expression was detected in all samples (100%); however, tumor samples exhibited significantly higher PSCA expression levels compared with the normal urothelium samples (P=0.038). PSCA mRNA expression was positively correlated with the histological grade of the tumor (G1-2 vs. G3; P=0.001); however, no significant difference was detected between patients with superficial (Ta or T1) and muscle-invasive (≥pT2) tumors (P=0.250). Thus, PSCA mRNA expression levels were associated with TCC and tumor histological grade, but not the tumor stage. Additionally, PSCA mRNA expression levels were significantly higher in T allele carriers compared with CC homozygous patients (P=0.001), indicating that the presence of the T allele may increase PSCA mRNA expression. Therefore, rs2294008 (C>T) may be associated with the biological properties of TCC and, thus, future research should focus on the physiological function of PSCA and the mechanism of rs2294008.

[Relationship between genetic polymorphism of NAT2 and susceptibility to urinary bladder cancer].

OBJECTIVE: To study the relationship between genetic polymorphism of NAT2 and susceptibility to bladder cancer. METHODS: NAT2 genotypes were determined by PCR-RFLP method in 69 patients with bladder transitional cell carcinoma and 88 healthy controls. RESULTS: The frequency of NAT2 slow genotypes was 26.1% (18/69) in patients compared with 14.8% (13/88) in controls (P < 0.05). Bladder cancer risk in patients with NAT2 slow genotypes was 2 fold as high as that in patients with NAT2 rapid genotypes. When NAT2 rapid genotypes/non-smoker were used as reference, bladder cancer risk increased to 5.8-fold (P < 0.05). Among the smokers with PY higher than 10, the patients showed a higher frequency of NAT2 slow genotype than controls (P < 0.05). It was also shown that the patients with slow NAT2 genotypes were more likely to have high grade tumor (P < 0.05) and advanced stage tumor (P < 0.01). CONCLUSION: The results suggest that NAT2 genetic polymorphism is associated with bladder cancer susceptibility. People with NAT2 slow genotype have higher bladder cancer risk.

[Expression of androgen receptor isoforms in normal human prostate].

OBJECTIVE: To investigate the expression of androgen receptor (AR) isoforms in normal human prostate. METHODS: Fourteen normal prostatic specimens from donors, aged 25 on average (21-28 yr), were analyzed by high resolution isoelectric focusing (IEF). The expression of AR isoforms was demonstrated in all 14 normal human prostatic tissues. RESULTS: Four types of AR isoforms were detected with isoelectric point value at 6.5, 6.0, 5.8 and 5.3 in 14 prostatic specimens. Binding of 3H-dihydrotestosterone (DHT) to these four AR isoforms was inhibited by the addition of 100-fold excess of DHT and testosterone. No effect of progesterone, estradiol and diethylstilbestrol on tritiated hormone binding was observed. CONCLUSIONS: There are four AR isoforms in normal human prostate. The expression of AR isoforms is different from one another.

Laparoscopic retroperitoneal dismembered pyeloplasty: single-center experience in China.

OBJECTIVE: To report on our experience with laparoscopic retroperitoneal dismembered pyeloplasty in the treatment of ureteropelvic junction (UPJ) obstruction. Special attention was paid to the technical features associated with the procedure. SUBJECTS AND METHODS: From May 2004 to April 2012, in total, 117 consecutive patients (64 men and 53 women) with a mean age of 33.5 years (range, 12-60 years) underwent laparoscopic retroperitoneal dismembered pyeloplasty for symptomatic and radiologically proved UPJ obstruction. Follow-up studies were performed with diuretic renography at 3 and 6 months postoperatively and annually thereafter. Success was defined as symptomatic relief and improvement of the diuresis renogram without evidence of obstructed drainage. RESULTS: The mean operative time was 170 minutes (range, 90-310 minutes), and the mean estimated blood loss was 40 mL (range, 20-100 mL). Crossing vessels were encountered in 21 patients (18.0%). In all cases, the ureter was transposed anteriorly. From 9 patients, including 4 cases of horseshoe kidney, coexisting renal calculi were successfully removed. The mean hospital stay was 7 days (range, 5-14 days). There were no intraoperative complications. Postoperative complication was recorded in 2 patients with leakage at the anastomosis. Seven patients developed anastomotic strictures, which required open surgery or ureteral stent. The success rate was 94% (110/117) at a mean follow-up of 43 months (range, 3-95 months). CONCLUSIONS: In our experience, laparoscopic retroperitoneal dismembered pyeloplasty is effective and feasible. With the improvement of technique, we believe that it would become a new standard treatment for UPJ obstruction.