Clear cell and non-clear cell renal cell carcinoma in young adults: clinicopathological features, survival outcomes and prognostic factors.

OBJECTIVES: Renal cell carcinoma (RCC) is infrequent among young adults. Few studies reported the outcome of RCC in young adults by pathological subtypes. The purpose of this study was to explore the clinicopathological features, survival outcomes and prognostic factors of young adult patients with clear cell (CCRCC) and non-clear cell renal cell carcinoma (NCCRCC). METHODS: This study included young adult patients aged 18-40 years who were diagnosed as renal cell carcinoma (RCC) between 2012 and 2022 at Peking University Third Hospital. All patients underwent either partial nephrectomy or radical nephrectomy, and some received adjuvant therapy. A comparative analysis was performed to investigate the differences in clinicopathological characteristics between the cohort of CCRCC and NCCRCC. Kaplan-Meier survival analysis was utilized to plot survival curves for young adults with RCC. The univariate and multifactorial prognostic analyses were conducted using the log-rank test and COX proportional hazards model. RESULTS: A total of 300 RCC patients aged 18-40 years were performed, of which 201 were diagnosed with CCRCC (67%) and 99 were diagnosed with NCCRCC(33%). The NCCRCC included 29 cases (9.7%) of chromophobe RCC, 28 cases (9.3%) of MiT family translocation RCC, 22 cases (7.3%) of papillary RCC, 11 cases (3.7%) of low malignant potential multifocal cystic RCC, and 6 cases of unclassified RCC (2.0%), 2 cases of mucinous tubule and spindle cell carcinoma (0.7%), and 1 case of FH-deficient RCC (0.3%).The mean age was 33.4 ± 6.1 years old. The overall and progression free 5-year survival rate was 99.1 and 95.3%, respectively. The NCCRCC cohort demonstrated a statistically significant decrease in progression-free survival (PFS) rate when compared to the CCRCC cohort (p < 0.001). There was no statistically significant difference observed in overall survival (OS) (p = 0.069). Pathological stage was a significant independent predictor for OS (p = 0.045). Pathological stage and nuclear grade were both independent predictors for PFS (p = 0.020; p = 0.005). CONCLUSIONS: The clinical and pathological features of young adults diagnosed with CCRCC exhibit notable distinctions from those of NCCRCC patients. The survival outcome was significantly influenced by the pathological stage, while both the nuclear grade and pathological stage had a significant impact on tumor progression. This study offered significant contributions to the understanding of the clinicopathological characteristics and prognostic determinants of renal cell carcinoma (RCC) in young adults.

Sperm retrieval rate and patient factors in azoospermia factor c microdeletion azoospermia: a systematic review.

OBJECTIVE: To reveal the overall sperm retrieval rate (SRR) and range in patients with azoospermia factor c (AZFc) microdeletion azoospermia by microdissection testicular sperm extraction (mTESE) and discuss the differences of preoperative patient factors among studies with various SRRs. PATIENTS AND METHODS: We searched PubMed, Web of Science and Embase until February 2023. All studies reporting SRRs by mTESE and required parameters of patients with AZFc microdeletions were included. The primary outcome was the SRR and, if available, the pregnancy rate (PR) and live-birth rate (LBR) after intracytoplasmic sperm injection were also investigated as secondary outcomes. RESULTS: Eventually 11 cohort studies were included in this review. A total number of 441 patients underwent mTESE and in 275 of them sperm was obtained, reaching an overall SRR of 62.4%. The SRRs among studies had a wide range from 25.0% to 85.7%. The studies reporting higher SRRs generally had older mean ages, and higher follicle-stimulating hormone and testosterone levels. Only four studies provided practical data on pregnancies and live-born children of patients with AZFc microdeletions, so the overall PR and LBR were unavailable. CONCLUSIONS: The overall SRR of patients with AZFc microdeletion azoospermia was 62.4%. The effect of patient factors in SR needs further evidence in future work.

Causal inference between rheumatoid arthritis and prostate cancer.

It is unclear if the association between rheumatoid arthritis (RA) and a higher risk of prostate cancer (Pca) reflects a causal relationship. We conducted a meta-analysis and used the Mendelian randomization method (MR) to evaluate the association between RA and Pca risk. A meta-analysis and subgroup analysis of the incidence of Pca in patients with RA was conducted. To determine whether genetically elevated RA levels were causally linked to Pca, two MR samples were employed. To eliminate gender-related bias, we conducted a stratified analysis of the GWAS data for RA by gender, specifically including 140,254 males. Additional MR analysis was also performed to determine potential confounding factors influencing the association between genetically susceptible RA and Pca. In total, 409,950 participants were enrolled in 20 trials to investigate the Pca risk in patients with RA. The meta-analysis suggested that RA was unrelated to the Pca risk (SIR = 1.072, 95% CI, 0.883-1.261). However, a subgroup analysis showed that low smoking rates might increase the Pca risk in patients with RA by 24%. The MR analysis showed that increased genetic susceptibility to RA was related to a high Pca risk (OR = 36.20, 95%CI = 1.24-1053.12, P = 0.037). The causality estimation of MR-Egger, Weighted mode, Simple mode, and Weighted median method were similar in direction and magnitude. Although our meta-analysis found no correlation between RA and Pca risk, MR analyses supported a causal relationship between genetic susceptibility to RA and increased prostate risk. Early attention to Pca risk in patients with RA may be important for improving prognosis and mortality in such patients. Further research is needed to determine the etiology of RA attributed to Pca and its underlying mechanisms.

Systemic lupus erythematosus and prostate cancer risk: a pool of cohort studies and Mendelian randomization analysis.

BACKGROUND: Current observational studies suggest that there may be a causal relationship between systemic lupus erythematosus (SLE) and prostate cancer (PC). However, there is contradictory evidence. This study aimed to investigate and clarify the association between SLE and PC. METHODS: We searched PubMed, Embase, Web of Science, and Scopus until May 2022. A meta-analysis was conducted on the standard incidence rate (SIR) and 95% CI. Subgroup analysis was performed based on the follow-up duration, study quality, and appropriate SLE diagnosis. Mendelian randomization (MR) of the two samples was used to determine whether genetically elevated SLE was causal for PC. Summary MR data were obtained from published GWASs, which included 1,959,032 individuals. The results were subjected to sensitivity analysis to verify their reliability. RESULTS: In a meta-analysis of 79,316 participants from 14 trials, we discovered that patients with SLE had decreased PC risk (SIR, 0.78; 95% CI, 0.70-0.87) significantly. The MR results showed that a one-SD increase in genetic susceptibility to SLE significantly reduced PC risk (OR, 0.9829; 95% CI, 0.9715-0.9943; P = 0.003). Additional MR analyses suggested that the use of immunosuppressants (ISs) (OR, 1.1073; 95% CI, 1.0538-1.1634; P < 0.001), but not glucocorticoids (GCs) or non-steroidal anti-inflammatory drugs (NSAIDs), which were associated with increased PC risk. The results of the sensitivity analyses were stable, and there was no evidence of directional pleiotropy. CONCLUSIONS: Our results suggest that patients with SLE have a lower risk of developing PC. Additional MR analyses indicated that genetic susceptibility to the use of ISs, but not GCs or NSAIDs, was associated with increased PC risk. This finding enriches our understanding of the potential risk factors for PC in patients with SLE. Further study is required to reach more definitive conclusions regarding these mechanisms.

Outcomes of microsurgical vasoepididymostomy using intussusception technique: a systematic review and meta­analysis.

A systematic review and meta-analysis of microsurgical vasoepididymostomy (MVE) for treating epididymal obstructive azoospermia (EOA) with different intussusception techniques. We conducted a comprehensive literature search using PubMed, Embase, and the Cochrane Central Register of Controlled Trials, retained literature related to obstructive azoospermia or male infertility and vasoepididymostomy, proactively reviewed other relevant literature, supplemented valuable references, and excluded studies that did not use intussusception and where valuable statistical data were difficult to obtain. Event rate and risk ratio (RR) were estimated. Patency rates were investigated. The influence of motile sperms found in the epididymal fluid, anastomotic sides and sites on patency was evaluated. 273 articles were comprised in this analysis, and 25 observational studies were eventually included, with a total patient sample of 1400. The overall mean patency rate was 69.3% (95% confidence interval [CI] 64.6-73.6%; I2 = 63.735%). We conducted a meta-analysis of the factors affecting patency after microsurgical IVE, finding that the presence of motile sperms in epididymal fluid (RR = 1.52; 95% CI 1.18-1.97%; P = 0.001), anastomosing bilaterally (RR = 1.32; 95% CI 1.15-1.50%; P < 0.0001) and distally (RR = 1.42; 95% CI 1.09-1.85%; P = 0.009) lead to higher patency rates. IVE is an effective treatment for EOA. The presence of motile sperms found in the epididymal fluid, anastomosing bilaterally and distally are significantly correlated with higher patency rates.

The effect of BMI and age on the outcomes of microsurgical vasoepididymostomy: a retrospective analysis of 181 patients operated by a single surgeon.

To design a treatment plan for patients with epididymal obstruction, we explored the potential impact of factors such as body mass index (BMI) and age on the surgical outcomes of vasoepididymostomy (VE). In this retrospective study, 181 patients diagnosed with obstructive azoospermia (OA) due to epididymal obstruction between September 2014 and September 2017 were reviewed. All patients underwent single-armed microsurgical intussusception VEs with longitudinal two-suture placement performed by a single surgeon (KH) in a single hospital (Peking University Third Hospital, Beijing, China). Six factors that could possibly influence the patency rates were analyzed, including BMI, age, mode of anastomosis, site of anastomosis, and sperm motility and quantity in the intraoperative epididymal fluid. Single-factor outcome analysis was performed via Chi-square test and multivariable analysis was performed using logistic regression. A total of 159 (87.8%, 159/181) patients were followed up. The follow-up time (mean ± standard deviation [s.d.]) was 27.7 ± 9.3 months, ranging from 12 months to 48 months. The overall patency rate was 73.0% (116/159). The multivariable analysis revealed that BMI and age significantly influenced the patency rate (P = 0.008 and 0.028, respectively). Younger age (≤28 years; odds ratio [OR] = 3.531, 95% confidence interval [95% CI]: 1.397-8.924) and lower BMI score (<26.0 kg m-2; OR = 2.352, 95% CI: 1.095-5.054) appeared to be associated with a higher patency rate. BMI and age were independent factors affecting the outcomes of microsurgical VEs depending on surgical expertise and the use of advanced technology.

Imaging predictors for assessment of inferior vena cava wall invasion in patients with renal cell carcinoma and inferior vena cava tumor thrombus: a retrospective study.

BACKGROUND: Renal cell carcinoma (RCC) has the propensity to lead to venous tumor thrombus (VTT). Nephrectomy with tumor thrombectomy is an effective treatment option but is a technically challenging surgical procedure that is accompanied by a high rate of complications. The aims of this study were to investigate pre-operative imaging parameters for the assessment of inferior vena cava (IVC) wall invasion due to a tumor thrombus in patients with RCC and to identify predictors from the intra-operative findings. METHODS: Clinical and imaging data were collected from 110 patients who underwent nephrectomy with IVC tumor thrombectomy (levels I-IV) for RCC and IVC tumor thrombus at the Peking University Third Hospital between May 2015 and March 2018. Univariable and multivariable logistic regression and receiver operating characteristic curves were used to assess the correlations between pre-operative imaging features and intra-operative macroscopic invasions of the IVC wall by tumor thrombus. RESULTS: Among the 110 patients, 41 underwent partial or segmental resection of IVC. There were univariate associations of pre-operative imaging parameters that could be used to predict the need for IVC resection, including those of the Mayo classification, maximum anterior-posterior (AP) diameter of the renal vein at the renal vein ostium (RVo), maximum AP diameter of the VTT at the RVo and IVC occlusion. For the multivariable analysis, the AP diameter of the VTT at the RVo and IVC occlusion were associated with a significantly increased risk of invasion of the IVC wall by tumor thrombus. The optimum imaging thresholds included an AP diameter of the VTT at the RVo larger than 17.0 mm and the presence of IVC occlusion, with which we predicted invasions of the IVC wall requiring IVC resection. The probabilities of intra-operative IVC resection for patients without both independent factors, with an AP diameter of the VTT at the RVo larger than 17.0 mm, with IVC occlusion, and with both concurrent factors were 5%, 23%, 56%, and 66%, respectively. CONCLUSION: An increase in the AP VTT diameter at the RVo and the presence of complete occlusion of the IVC are independent risk factors for a high probability of IVC wall invasion by tumor thrombus.

ß-elemene attenuates macrophage activation and proinflammatory factor production via crosstalk with Wnt/ß-catenin signaling pathway.

ß-elemene, extracted from Rhizoma zedoariae, has been widely used as a traditional medicine for its antitumor activity against a broad range of cancers. However, the effect of ß-elemene in inflammation disorders has yet to be determined. The present study was designed to investigate the anti-inflammatory effects and potential molecular mechanisms of ß-elemene in lipopolysaccharide (LPS)-induced murine macrophage cells RAW264.7. We found that the production of pro-inflammatory mediators, including interleukin-6(IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), induced by LPS was significantly suppressed by ß-elemene in a dose-dependent manner in RAW264.7 macrophage cell line. Also, ß-elemene inhibited LPS-induced nitric oxide synthase (iNOS) and interleukin-10 (IL-10) expression by RAW264.7, which was related to the down-regulation of Wnt/ß-catenin signaling pathway. Importantly, this study demonstrates that ß-catenin was significantly inhibited by ß-elemene, which appeared to be largely responsible for the down-regulation of Wnt/ß-catenin signaling pathway. Accordingly, the deletion of ß-catenin in primary macrophages reversed ß-catenin-elicited inhibition of immune response. Furthermore, ß-catenin expression and Wnt/ß-catenin signaling pathway induced by LPS in RAW264.7 was also significantly inhibited by α-humulene, one isomeric sesquiterpene of ß-elemene. α-humulene was also found to significantly inhibit LPS-induced production of proinflammatory cytokines. However, α-humulene showed more cytotoxic ability than ß-elemene. Collectively, our data illustrated that ß-elemene exerted a potent inhibitory effect on pro-inflammatory meditator and cytokines production via the inactivation of ß-catenin, and also demonstrated the protective functions of ß-elemene in endotoxin-induced inflammation. ß-elemene may serve as potential nontoxic modulatory agents for the prevention and treatment of inflammatory diseases.