Development and validation of a model for predicting the risk of prostate cancer.

BACKGROUND: Abnormal hematologic parameters before patients undergoing prostate biopsy play a pivotal role in guiding the surgical management of prostate cancer (PCa) incidence. This study aims to establish the first nomogram for predicting PCa risk for better surgical management. METHODS: We retrospectively reviewed and analyzed the data including basic information, preoperative hematologic parameters, and imaging examination of 540 consecutive patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsy for elevated prostate-specific antigen (PSA) in our medical center between 2017 and 2021. Logistic regression analysis was used to determine the risk factors for PCa occurrence, and the nomogram was constructed to predict PCa occurrence. Finally, the data including 121 consecutive patients in 2022 were prospectively collected to further verify the results. RESULTS: In retrospective analyses, univariate and multivariate logistic analyses identified that three variables including age, diabetes, and De Ritis ratio (aspartate transaminase/alanine transaminase, AST/ALT) were determined to be significantly associated with PCa occurrence. A nomogram was constructed based on these variables for predicting the risk of PCa, and a satisfied predictive accuracy of the model was determined with a C-index of 0.765, supported by a prospective validation group with a C-index of 0.736. The Decision curve analysis showed promising clinical application. In addition, our results also showed that the De Ritis ratio was significantly correlated with the clinical stage of PCa patients, including T, N, and M stages, but insignificantly related to the Gleason score. CONCLUSIONS: The increased De Ritis ratio was significantly associated with the risk and clinical stage of PCa and this nomogram with good discrimination could effectively improve individualized surgical management for patient underdoing prostate biopsy.

Pan-cancer analysis identifies SPEN mutation as a predictive biomarker with the efficacy of immunotherapy.

The association between specific genetic mutations and immunotherapy benefits has been widely known, while such studies in pan-cancer are still limited. SPEN, mainly involved in X chromosome inactivation (XCI), plays an essential in tumorigenesis and sex differences in cancer. Thus, we firstly analyzed the potential role of SPEN in the TCGA pan-cancer cohort and clinical samples. Bioinformatics analysis and immunohistochemistry (IHC) staining confirm that the expression of SPEN is significantly different in various cancers and may involve RNA splicing and processing via enrichment analysis. Then, our data further revealed that those patients with SPEN mutation could predict a better prognosis in pan-cancer and had distinct immune signatures, higher tumor mutation burden (TMB), and microsatellite instability (MSI) in common cancer types. Finally, the cancer patients from 9 studies treated with immune checkpoint inhibitors were included to investigate the efficacy of immunotherapy. The results further showed that SPEN mutation was associated with better clinical outcomes (HR, 0.74; 95%CI, 0.59-0.93, P = 0.01), and this association remained existed in female patients (HR, 0.60; 95%CI, 0.38-0.94 P = 0.024), but not in male patients (HR, 0.82; 95%CI, 0.62-1.08 P = 0.150). Our findings demonstrated that SPEN mutation might strongly predict immunotherapy efficacy in pan-cancer.

Cholelithiasis increased prostate cancer risk: evidence from a case-control study and a meta-analysis.

INTRODUCTION: Cholelithiasis represents a known risk factor for digestive system neoplasm. Few studies reported the association between cholelithiasis and the risk of prostate cancer (PCa), and the results were controversial. METHODS: We reviewed the medical records of the Second Affiliated Hospital of Chongqing Medical University Hospital to perform a retrospective matched case-control study, which included newly diagnosed 221 PCa patients and 219 matched controls. Logistic regression was applied to compare cholelithiasis exposure and adjusted for confounding factors. Additionally, we conducted a meta-analysis pooling this and published studies further to evaluate the association between cholelithiasis and PCa risk. Related ratio (RR) and 95% confidence interval (95%CI) were used to assess the strength of associations. RESULTS: Our case-control study showed that cholelithiasis was associated with a higher incidence of PCa (OR = 1.87, 95% CI: 1.06-3.31) after multivariable adjustment for covariates. The incidence of PCa was increased in patients with gallstones but not cholecystectomy. 7 studies involving 80,403 individuals were included in the meta-analysis. Similarly, the results demonstrated that cholelithiasis was associated with an increased risk of PCa (RR = 1.35, 95%CI: 1.17-1.56) with moderate-quality evidence. Cholelithiasis patients with low BMI increased the PCa incidence. Moreover, Subgroup analysis based on region showed that cholelithiasis was associated with PCa in Europe (RR = 1.24, 95%CI 1.03-1.51) and Asia (RR = 1.32, 95%CI 1.24-1.41). CONCLUSIONS: The results suggested an association between cholelithiasis and the risk of PCa. There was no significant relationship between cholecystectomy therapy and PCa risk. Further cohort studies should be conducted to demonstrate the results better.

Retrospective analysis of the changes in the surgical treatment of benign prostatic hyperplasia during an 11-year period: a single-center experience.

The present study aimed to determine whether the number of patients with symptomatic benign prostatic hyperplasia (BPH) who preferred surgery decreased during the past 11 years at our center (West China Hospital, Chengdu, China), and whether this change affected the timing of surgery and the physical condition of surgical patients. This retrospective study included 57 557 patients with BPH treated from January 2008 to December 2018. Of these, 5427 patients were treated surgically. Surgical patients were divided into two groups based on the time of treatment (groups 8-13 and groups 13-18). The collected data comprised the percentage of all patients with BPH who underwent surgery, baseline characteristics of surgical patients, rehabilitation time, adverse events, and hospitalization costs. The surgery rates in groups 8-13 and groups 13-18 were 10.5% and 8.5% (P < 0.001), respectively. The two groups did not clinically differ regarding patient age and prostate volume. The rates of acute urinary retention and renal failure decreased from 15.0% to 10.6% (P < 0.001) and from 5.2% to 3.1% (P < 0.001), respectively. In groups 8-13 and groups 13-18, the mean catheterization times were 4.0 ± 1.7 days and 3.3 ± 1.6 days (P < 0.001), respectively, and the mean postoperative hospitalization times were 5.1 ± 2.4 days and 4.2 ± 1.8 days (P < 0.001), respectively. The incidences of unplanned second surgery and death reduced during the study period. The surgery rate decreased over time, which suggests that medication was chosen over surgery. However, the percentage of late complications of BPH also decreased over time, which indicates that the timing of surgery was not delayed.

Transurethral resection of ejaculatory duct combined with seminal vesiculoscopy for management of persistent or recurrent hemospermia in men with ejaculatory duct obstruction.

BACKGROUND: Persistent or recurrent haemospermia often occurs in individuals with ejaculatory duct obstruction (EDO). This study aimed to evaluate the efficacy and safety of transurethral resection of the ejaculatory duct (TURED) combined with seminal vesiculoscopy in treating persistent or recurrent haemospermia in men with EDO. METHODS: From June 2014 to March 2018, 103 consecutive patients with EDO who underwent TURED combined with seminal vesiculoscopy for persistent or recurrent haemospermia at the Department of Urology of West China Hospital were enrolled into this retrospective study. The patients were evaluated mainly by detailed history-taking and performing semen analysis, transrectal ultrasonography, and magnetic resonance imaging. RESULTS: Among the 103 patients, 79 (76.70%) had cysts of the lower male genitourinary tract; 63 (61.17%) had blood clots; and 32 (31.07%) had calculi in the seminal vesicle and/or prostatic utricle. The duration of postoperative follow-up was 12 months, and the symptoms of haemospermia disappeared in 96 (93.20%) patients. There was no significant difference in the semen PH and sperm count before and after surgery; however, the ejaculate volume and sperm motility significantly improved postoperatively. Except for two cases of acute urinary retention and one case of watery ejaculate after surgery, no severe postoperative complications, including epididymitis, urethral stricture, urinary incontinence, retrograde ejaculation, or rectal injury, were observed. CONCLUSION: TURED combined with seminal vesiculoscopy is a suitable method for the diagnosis and treatment of persistent or recurrent haemospermia in men with EDO.

The aldosterone index could be used to diagnose the dominant gland in primary aldosteronism - a retrospective study.

INTRODUCTION: Failed cannulation in the right adrenal vein, which makes the sampling results in the contralateral vein and inferior vena cava (IVC) nonsense, is the main obstacle of using adrenal vein sampling (AVS) in the lateralisation diagnosis in primary aldosteronism (PA). We performed a retrospective study to evaluate the specificity and sensitivity of using the aldosterone index (AI) in PA lateralisation diagnosis. MATERIAL AND METHODS: We enrolled 116 patients who were diagnosed with PA and then underwent AVS in the West China Hospital of Sichuan University from April 2015 to April 2017. The AI, calculated by dividing the aldosterone concentration of the failed side by the aldosterone concentration of IVC, was used for lateralisation diagnosis if the cannulation was judged to be failed by traditional method. Patients with dominant adrenal gland based on successful AVS were included in subgroup 2 (n = 75), while the patients diagnosed with a dominant gland using AI method were enrolled in subgroup 1 (n = 41). RESULTS: No significant difference of clinical and biochemical findings between the two groups was detected (p value after operation > 0.05). ROC analysis was performed to test the specificity and sensitivity based on the AI in subgroup 2. The AUC for dominant gland detection was 0.76, which resulted in 91.3% sensitivity and 67.53% specificity. The positive and negative likelihood ratios were 2.81. CONCLUSIONS: Our data suggested that the modified strategy using AI to diagnose the dominant gland in PA is an efficient method when cannulation has failed in the right side.

First-degree family history of breast cancer is associated with prostate cancer risk: a systematic review and meta-analysis.

BACKGROUND: The relationship between first-degree family history of female breast cancer and prostate cancer risk in the general population remains unclear. We performed a meta-analysis to determine the association between first-degree family history of female breast cancer and prostate cancer risk. METHODS: Databases, including MEDLINE, Embase, and Web of Science, were searched for all associated studies that evaluated associations between first-degree family history of female breast cancer and prostate cancer risk up to December 31, 2018. Information on study characteristics and outcomes were extracted based on the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. The quality of evidence was assessed using the GRADE approach. RESULTS: Eighteen studies involving 17,004,892 individuals were included in the meta-analysis. Compared with no family history of female breast cancer, history of female breast cancer in first-degree relatives was associated with an increased risk of prostate cancer [relative risk (RR) 1.18, 95% confidence interval (CI) 1.12-1.25] with moderate-quality evidence. A history of breast cancer in mothers only (RR 1.19, 95% CI 1.10-1.28) and sisters only (RR 1.71, 95% CI 1.43-2.04) was associated with increased prostate cancer risk with moderate-quality evidence. However, a family history of breast cancer in daughters only was not associated with prostate cancer incidence (RR 1.74, 95% CI 0.74-4.12) with moderate-quality evidence. A family history of female breast cancer in first-degree relatives was associated with an 18% increased risk of lethal prostate cancer (95% CI 1.04-1.34) with low-quality evidence. CONCLUSIONS: This review demonstrates that men with a family history of female breast cancer in first-degree relatives had an increased risk of prostate cancer, including risk of lethal prostate cancer. These findings may guide screening, earlier detection, and treatment of men with a family history of female breast cancer in first-degree relatives.

Association between TP53 gene codon72 polymorphism and prostate cancer risk: A systematic review and meta-analysis.

BACKGROUND: TP53 gene polymorphism could increase risks of several kinds of cancer. But it remained controversial whether TP53 gene codon72 polymorphism was associated with the susceptibility to prostate cancer. Thus, we conducted a meta-analysis that evaluated the association between TP53 gene codon72 polymorphism and prostate cancer risk. METHOD: A comprehensive research was performed from PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI) up to December 31, 2018. A random effect model was used to evaluate the effect of the outcome. The statistical analyses were performed with Review Manager 5.3.0 and Stata 14.0. The sensitivity analysis and publication bias tests were also performed to confirm the reliability of this meta-analysis. RESULTS: 22 studies included 3146 cases and 4010 controls were involved in this meta-analysis. Overall, no association was observed between TP53 gene codon72 polymorphism and prostate cancer risk (Arg vs Pro: odds ratio [OR] = 1.12, 95% confidence interval [CI] = 0.98-1.30; ArgArg vs ProPro: OR = 1.26, 95% CI = 0.90-1.75; ProPro vs ArgArg+ ArgPro: OR = 1.17, 95% CI = 0.86-1.57; ArgPro+ ProPro vs ArgArg: OR = 1.21, 95% CI = 0.97-1.51). Subgroup analyses, based on ethnicity, source of control and Hardy-Weinberg equilibrium (HWE) status, showed consistent results. CONCLUSION: The meta-analysis we performed showed that there was no association of TP53 gene codon72 polymorphism with prostate cancer risk.

Contribution of prostate stem cell antigen variation rs2294008 to the risk of bladder cancer.

OBJECTIVE: Number of studies have been performed to evaluate the relationship between prostate stem cell antigen (PSCA) variation rs2294008 and bladder cancer risk, but the sample size was small and the results were conflicting. This meta-analysis was conducted to comprehensively evaluate the overall association. METHODS: Pubmed, Web of science, Embase, China biology medical literature database (CBM), China National Knowledge Infrastructure (CNKI), Wan Fang and Weipu databases were searched before June 30, 2018. The strength of associations was assessed using odds ratios (ORs) and 95% confidence intervals (CIs). All of the statistical analyses were conducted using Review Manager 5.3 and Stata 14.0. RESULTS: Ten studies involved 14,021 cases and 26,871 controls. Overall, significant association was observed between the PSCA gene variant rs2294008 polymorphism and bladder cancer (T vs C: OR = 1.16, 95%CI = 1.12-1.20; TT vs CC: OR = 1.32, 95%CI = 1.24-1.41; TT vs CT+CC: OR = 1.15, 95%CI = 1.09-1.22; TT+CT vs CC: OR = 1.27, 95%CI = 1.21-1.34). In subgroup analysis by ethnic group, a statistically significant association was observed in Asians (T vs C: OR = 1.23, 95%CI = 1.15-1.31) and Caucasians (T vs C: OR = 1.14, 95%CI = 1.10-1.18). The sensitivity analysis confirmed the reliability and stability of the meta-analysis. CONCLUSION: Our meta-analysis supports that the PSCA gene variant rs2294008 polymorphism might contribute to individual susceptibility to bladder cancer.

Meta-analysis of the association between the inflammatory potential of diet and urologic cancer risk.

BACKGROUND: The inflammatory potential of diet has been shown to have an association with the risk of several cancer types, but the evidence is inconsistent regarding the related risk of urologic cancer (UC). Therefore, we conducted the present meta-analysis to investigate the association between the inflammatory potential of diet and UC. METHODS: PubMed, Embase and Web of Science were searched up to July 31, 2018. Two reviewers independently selected the studies and extracted the data. The pooled risk ratio (RR) and its 95% confidence interval (CI) were calculated using the Stata12.0 software package. RESULTS: Nine case-control studies and three cohort studies including 83,197 subjects met the inclusion criteria. The overall meta-analysis results showed that individuals with the highest category of DII (dietary inflammatory index) were associated with an increased risk of prostate cancer (RR = 1.62, 95% CI: 1.30-2.02); subgroup analysis showed consistent results. For kidney and bladder cancer, significant positive associations were found in individuals with the highest category of DII score; however, no significant association was found between DII and the risk of urothelial cell carcinoma (UCC). CONCLUSION: Available data suggest that more pro-inflammatory diets are associated with an increased risk of prostate cancer, kidney cancer and bladder cancer. However, further well designed large-scaled cohort studies are warranted to provide more conclusive evidence.

TP53 gene Arg72Pro polymorphism and male infertility risk: A meta-analysis.

To evaluate the association between TP53 codon72 polymorphism and male infertility risk. We conducted a search on Medline, Embase, Web of Science and CNKI up to April 30, 2017. Odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the strength of the association. Seven studies including 1,818 cases and 2,278 controls met the inclusion criteria. The pooled results indicated that no significant association was observed between TP53 codon72 polymorphism and male infertility risk (G versus C: OR = 1.11, 95%CI = 0.94-1.32; GG versus CC: OR = 1.26, 95%CI = 0.90-1.78; GG versus GC+CC: OR = 1.16, 95%CI = 0.90-1.49; GG+GC versus CC: OR = 1.15, 95%CI = 0.88-1.49). In the subgroup analysis by ethnicity, significant association was observed between TP53 codon72 polymorphism and male infertility risk in non-Chinese (G versus C: OR = 1.47, 95%CI = 1.14-1.89), but not in Chinese population (G versus C: OR = 1.03, 95%CI = 0.87-1.22). In conclusion, this study suggested that TP53 codon72 polymorphism might be associated with an increased susceptibility to male infertility in non-Chinese population, but not in Chinese population. Studies with larger sample sizes and representative population-based cases and well-matched controls are needed to validate our results.

[Growth Regulation of Factor Inhibiting Hypoxia-Inducible Factor in Renal Carcinoma Cells].

OBJECTIVE: To detect the expression and growth regulation effects of the factor inhibiting hypoxia-inducible factor (FIH-1) in renal carcinoma cells. METHODS: The expressions of FIH-1,hypoxia inducible factor (HIF) and vascular endothelial growth factor (VEGF) were examined in OS-RC-2 and 786-0 cell lines via real-time PCR (RT-PCR) and Western blot. Overexpression plasmid of FIH-1 were designed and constructed as EX-V1104-M45-FIH-1. After the transfection of the plasmid into OS-RC-2 and 786-0 cells,the expression levels of FIH-1,HIF and VEGF were measured by RT-PCR and Western blot,while cell proliferation was tested by MTT. RESULTS: The expressions of FIH-1,HIF-1α,HIF-2α and VEGF were detected in OS-RC-2 cells,and FIH-1,HIF-2α and VEGF were detected in 786-0 cells. After the transfection of EX-V1104-M45-FIH-1, the level of FIH-1 was increased in OS-RC-2,while the levels of HIF-2α,HIF-1α and VEGF were decreased. MTT showed that FIH-1 plasmid transfection decreased the cell proliferation of OS-RC-2,but did not show inhibition on 786-0 cells proliferation. CONCLUSION: FIH-1/HIF-1α/VEGF signaling pathway exists in renal carcinoma cell lines.

[Genetic characteristics of varicocele: An almost unexplored area].

Varicocele (VC) is a most common risk factor of male infertility and its etiology, however, remains rarely explored. Some researchers reported the genetic predisposition of VC, showing that its prevalence was 3－8 times higher in the first-degree relatives of the patients than in the controls. Studies on the genetic characteristics of VC are relatively rare, only a few relating its association with single nucleotide polymorphisms (SNP). The onset of VC is known to be related to venous varicosity (VV) in the lower extremity, and the two conditions have similar pathogenesis and clinical features. Several studies confirmed the association of the onset of VV with some SNPs, such as the essential transcription factor for the formation of venous valves and vascular development FOXC2, the gene of vascular endothelial growth factor A (VEGFA), and its receptor gene VEGFR2. The mechanisms of the SNPs affecting VV in the lower extremity are similar to the pathogenesis of VC, which may shed some light on the etiology of VC. The exploration of the genetic characteristics of VC is of much significance for the early prevention and precision therapy of diseases, and an insight into the correlation between VC and lower extremity VV may afford some valuable clues to studies on the genetic characteristics of VC.

[Minimally invasive surgery for ejaculatory duct obstruction in infertile men].

Ejaculatory duct obstruction(EDO) accounts for 1- 5% of the causes of male infertility and can be corrected by various surgical methods,among which transurethral resection of the ejaculatory ducts(TURED) is considered as the gold standard for its treatment and has been well established in clinical practice. Transutricular seminal vesiculoscopy has been gaining more and more attention for its cost-effectiveness and few complications in the treatment of EDO. The clinical evidence for treating EDO by balloon dilatation and seminal vesicle lavage is limited and its application value needs to be further investigated. This paper presents an overview on the treatment of EDO in infertile men by minimally invasive surgery.

Contribution of Macrophage Migration Inhibitory Factor -173G/C Gene Polymorphism to the Risk of Cancer in Chinese Population.

BACKGROUND: Macrophage migration inhibitory factor (MIF) -173G/C (rs755622) gene polymorphism has been associated with cancer risk. Previous studies have revealed that MIF -173G/C gene polymorphism may increase cancer in the Chinese population, while results of individual published studies remain inconsistent and inconclusive.We performed this meta-analysis to derive a more precise estimation of the relationship. MATERIALS AND METHODS: We conducted a search on PubMed, Embase, MEDLINE, Cochrane Library ,Chinese National Knowledge Infrastructure (CNKI), Wanfang, Weipu on Dec 31, 2014.Odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the association. A total of eight studies including 2,186 cases and 2,285 controls were involved in this meta-analysis. RESULTS: The pooled results indicated the significant association between MIF -173G/C polymorphism and the risk of cancer for Chinese population (CC + CG vs GG: OR=1.14, 95%CI=1.02-127, pheterogeneity<0.01; P =0.023; CC vs CG+GG: OR=1.12, 95%CI=1.02- 1.23, pheterogeneity< 001; P =0.017;CC vs GG: OR=1.18, 95%CI=1.04-1.33, pheterogeneity<001; P =0.008; CG vs GG:OR=1.03, 95%CI=0.91-1.15, pheterogeneity<001; P =0.656; C vs G:OR=1.24, 95%CI=1.14-1.25, pheterogeneity<001; P <001). Subgroup analysis showed that in patients with "solid tumors", heterogeneity was very large (OR=0.94,95%CI=0.83-1.06,pheterogeneity=0.044; p=0.297). Within "non-solid tumors", the association became even stronger (OR=6.62, 95 % CI=4.32-10.14, pheterogeneity<0.001; p <0.001). CONCLUSIONS: This study suggested that MIF ?173G/C gene polymorphism may increase increase cancer in the Chinese population.Furthermore, more larger sample and representative population-based casees and well-matched controls are needed to validate our results.