Urology research center journal club: articles presentation 2024.02.12 (1402.11.23)

Journal Club 2024.02.12 (1402.11.23)

1- Dr. Mohamadi: Predictive value of prostate calcification for future cancer occurrence: a retrospective long-term follow-up cohort study

https://doi.org/10.1259/bjr.20221110

Although prostate calcification is often identified on pelvic CT images, calcification itself is usually not considered clinically significant. A recent histological study proposed an association between prostate calcification and prostate cancer occurrence. Our aim was to determine the predictive value of prostate calcifications for future prostate cancer occurrence. We retrospectively analysed male patients (≥50 years old) without prior prostate cancer history, who underwent unenhanced pelvic CT between April 2010 and March 2011, and followed-up until December 2021. Cox proportional hazards models were used to assess prostate cancer risk with prostate calcification (defined as a high-density area larger than 3 mm with CT attenuation values ≥ 130 HU), controlling for age, body mass index (BMI), hypertension and diabetes mellitus. A total of 636 male patients (mean age, 68 years ± 9 [standard deviation]) were evaluated. At the end of follow-up, prostate cancer had been more frequently diagnosed in patients with prostate calcification than those without prostate calcification (6.5% vs  2.6%). Multivariate analysis revealed that prostate calcification on CT was a significant predictor of future prostate cancer occurrence (hazard ratio [HR], 2.7; 95% CI: 1.20, 5.91; p = 0.016). No statistical differences were observed in any other factors. Prostate calcification may be a significant predictor of future prostate cancer occurrence, and may be used for risk stratification and to guide screening protocols.

2- Dr.Najarzadegan: Prospective comparison of extracorporeal shock wave lithotripsy and ureteroscopy in distal ureteral stones

https://link.springer.com/article/10.1007/s00240-023-01460-4

The optimal treatment modality of distal ureteral stones is controversial. Therefore, we conducted a prospective study to evaluate the efficacy, safety, and cost of early second shock wave lithotripsy (SWL) sessions versus ureterorenoscopy (URS) in patients with distal ureteral stones. This prospective study was conducted in a tertiary hospital from June 2020 to April 2022. Patients who underwent SWL or URS for distal ureteral stones were enrolled in this study. The stone-free rate (SFR), secondary treatment rate, complications, and costs were recorded. Propensity-score matching (PSM) analysis was also performed. A total of 1023 patients were included, of whom 68.4% (700) were treated with SWL and 31.6% (323) with URS. Based on PSM, SWL had an equivalent SFR (87.4% vs. 84.9%, P = 0.325) at one month after SWL and secondary treatment rate (10.7% vs.10.8%, P = 0.958) when compared with URS. Complications were rare and comparable between the SWL and URS groups (6.0% vs. 5.9%, P > 0.05), while the incidence of ureteral injuries (i.e., perforations) was higher in the URS group compared with the SWL group (1.3% vs. 0%, P = 0.019). The hospital stay was significantly shorter (1 day vs. 2 days, P < 0.001) and the costs considerably less (2000 RMB vs. 25,030 RMB; P < 0.001) in the SWL group compared with the URS group. This prospective study demonstrated that early second SWL sessions had equivalent efficacy in addition to reduced complication rates and costs compared with URS in patients with distal ureteral stones. Our findings may help guide clinical decision making.

3- Dr.Alphil: USP54 is a potential therapeutic target in castration-resistant prostate cancer

https://bmcurol.biomedcentral.com/articles/10.1186/s12894-024-01418-7

USP54, a ubiquitin-specific protease in the deubiquitinase (DUB) family, facilitates the malignant progression of several types of cancer. However, the role of USP54 in prostate cancer (PCa), especially castration-resistant prostate cancer (CRPC), remains unknown. We established the CRPC LNCaP-AI cell line from the hormone-sensitive prostate cancer (HSPC) LNCaP cell line. RNA-Seq was utilized to explore DUB expression levels in LNCaP and LNCaP-AI. USP54 was knocked down, and its effects on cell growth were evaluated in vitro and in vivo. Bioinformatics analyses were conducted to explore signaling pathways affected by USP54 in PCa. Quantitative polymerase chain reaction was used to confirm key signaling pathways involved. USP54 was the most strongly upregulated DUB in LNCaP-AI cells compared with LNCaP cells. USP54 levels were higher in PCa than in normal tissues. USP54 silencing suppressed the proliferation of PCa cell lines, both in vitro and in vivo. USP54 expression was positively correlated with the androgen receptor (AR) signaling level in PCa samples, and USP54 knockdown inhibited AR signaling in PCa cells. USP54 was upregulated during HSPC progression to CRPC. USP54 depletion suppressed CRPC cell proliferation both in vitro and in vivo. USP54 may facilitate PCa progression by regulating AR signaling.

4- Dr.Ghiasi: PROSPECTIVE RANDOMIZED COMPARISON OF TRANSPERITONEAL VERSUS RETROPERITONEAL LAPAROSCOPIC RADICAL NEPHRECTOMY

https://doi.org/10.1097/01.ju.0000145886.26719.73

We report on a prospective randomized comparison of transperitoneal versus retroperitoneal laparoscopic radical nephrectomy for renal tumor. Between June 1999 and June 2001, 102 consecutive eligible patients with a computerized tomography identified renal tumor were prospectively randomized to undergo either a transperitoneal (group 1, 50 patients) or retroperitoneal (group 2, 52 patients) laparoscopic radical nephrectomy with intact specimen extraction. Exclusion criteria for the study included body mass index greater than 35 or a history of prior major abdominal surgery in the quadrant of interest. Both groups were matched regarding age (63 versus 65 years, p = 0.69), BMI (29 versus 28, p = 0.89), American Society of Anesthesiologists class (2.7 versus 2.8, p = 0.37), laterality (right side 46% versus 48%, p = 0.85) and mean tumor size (5.3 versus 5.0 cm, p = 0.73). All 102 procedures were technically successful without the need for open conversion. Compared to the transperitoneal approach, the retroperitoneal approach was associated with a shorter time to renal artery control (91 versus 34 minutes, p <0.0001), shorter time to renal vein control (98 versus 45 minutes, p <0.0001) and shorter total operative time (207 versus 150 minutes, p = 0.001). However, the transperitoneal and retroperitoneal approaches were similar in terms of estimated blood loss (180 versus 242 cc, p = 0.13), hospital stay (43 versus 45 hours, p = 0.55), intraoperative complications (10% versus 7.7%, p = 0.30), postoperative complications (20% versus 13.5%, p = 0.14) and postoperative analgesia requirements (27 versus 26 mg MSO4 equivalent p = 0.13). Pathology revealed renal cell carcinoma in 84% and 75% of cases, respectively, with no positive surgical margin in any case. Laparoscopic radical nephrectomy can be performed efficiently and effectively with the transperitoneal or the retroperitoneal approach. While renal hilar control and total operative time may be quicker with retroperitoneoscopy, the approaches are similar in terms of other patient outcomes evaluated.

5- Dr.Chivaei: Elafibranor emerged as a potential chemotherapeutic drug for non-muscle invasive bladder cancer

https://doi.org/10.1016/j.cellin.2024.100149

Intravesical infusion of chemotherapeutics is highly recommended by several clinical guidelines for treating nonmuscle invasive bladder cancer (NMIBC). However, cytotoxic chemotherapeutics can cause a series of side effects, which greatly limits their application. Herein, a starvation therapy strategy was proposed, and elafibranor (ELA) was validated as a safe chemotherapeutic for NMIBC. The results showed that 20 μM ELA was sufficient to inhibit the proliferation and migration of bladder cancer cells and increase the level of intracellular reactive oxygen species (ROS). Furthermore, 2 mg/kg ELA treatment blocked the growth of primary tumors in an immunodeficient model by inhibiting proliferation and inducing apoptosis and improved the survival time of immunocompetent model mice. ELA treatment up to 10 mg/kg met the general safety requirements. We also established a patient-derived conditional reprogramming cell (CRC) model to assess the clinical translational potential of ELA. The antitumor effect and antitumor specificity of ELA treatment were confirmed. This work not only identified a promising chemotherapeutic for NMIBC but also provided a potential methodological system for drug discovery.

6- Dr.Beiranvand: The urinary microbiome associated with bladder cancer

https://www.nature.com/articles/s41598-018-29054-w

Recent findings suggest that human microbiome can influence the development of cancer, but the role of microorganisms in bladder cancer pathogenesis has not been explored yet. The aim of this study was to characterize and compare the urinary microbiome of bladder cancer patients with those of healthy controls. Bacterial communities present in urine specimens collected from 12 male patients diagnosed with bladder cancer, and from 11 healthy, age-matched individuals were analysed using 16S sequencing. Our results show that the most abundant phylum in both groups was Firmicutes, followed by Actinobacteria, Bacteroidetes and Proteobacteria. While microbial diversity and overall microbiome composition were not significantly different between groups, we could identify operational taxonomic units (OTUs) that were more abundant in either group. Among those that were significantly enriched in the bladder cancer group, we identified an OTU belonging to genus Fusobacterium, a possible protumorigenic pathogen. In an independent sample of 42 bladder cancer tissues, 11 had Fusobacterium nucleatum sequences detected by PCR. Three OTUs from genera Veillonella, Streptococcus and Corynebacterium were more abundant in healthy urines. However, due to the limited number of participants additional studies are needed to determine if urinary microbiome is associated with bladder cancer.

7- Dr.Zemanati: Risk factors and predictors of urogenous sepsis after percutaneous nephrolithotomy for idiopathic calcium oxalate nephrolithiasis

doi: 10.21037/tau-23-219

The aim of this study was to use bioinformatics approaches to screen and identify the key genes of idiopathic calcium oxalate nephrolithiasis, and explore its potential molecular mechanism. The GSE73680 kidney stone data set was downloaded from the Gene Expression Omnibus (GEO). R software (The R Foundation for Statistical Computing) was used to screen differentially expressed genes. GeneMANIA and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) databases were used to analyze related genes interacting with crucial genes, and a protein-protein interaction (PPI) network was constructed. The differential genes were then subjected to the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. The clinical data of 156 patients who received percutaneous nephrolithotomy (PCNL) therapy at our facility between January 2013 and December 2017 were retrospectively analyzed. The various parameters associated with postoperative urogenous sepsis were identified using multivariable logistic regression analysis. The study discovered one differentially expressed gene was nucleotide-binding oligomerization domain-containing protein 2 (NOD2). GO and KEGG analysis showed that NOD2 might affect the occurrence of idiopathic calcium oxalate kidney stones by affecting inflammation, receptor expression, immune environment, necrosis, apoptosis, and other pathways. The clinical parameter of patients who participated in the study, including preoperative urinary white blood cell (WBC) count, preoperative urinary nitrite, stone diameter, operation time, WBC count, and WBC D values, were statistically different between the systemic inflammatory response syndrome (SIRS) group and the urosepsis group. According to multivariate logistic regression analysis, the preoperative urine nitrite, calculus diameter, blood WBC, and NOD2 expression 3 hours after surgery were all independently associated with the urosepsis development. Preoperative urinary nitrite positive status, postoperative WBC count ≥2.98×109/L 3 hours after operation, stone diameter >6 cm, and low expression of NOD2 in renal papillary tissue are more likely to cause the urinary source of idiopathic calcium oxalate nephrolithiasis after PCNL urogenous sepsis. These parameters also offer a viable treatment paradigm for the perioperative management of PCNL in treating idiopathic calcium oxalate kidney stones.

8- Dr.Karimian: Superior calyceal access vs. other calyceal access in percutaneous nephrolithotomy: A systematic review and meta-analysis

https://doi.org/10.3389/fsurg.2022.930159

To evaluate the superior calyceal access’s performance and safety in relation to other calyceal access during percutaneous nephrolithotomy (PCNL). The suggested reporting items for systematic reviews and meta-analysis were used to conduct this meta-analysis (PRISMA). To find pertinent studies for this meta-analysis, we searched PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI). Operation time and hospital stay are two secondary outcomes, whereas failed stone clearance and complication events are the two major outcomes. Utilizing Stata 15.0, RevMan 5.3, and R 4.0.2, relative data were extracted and evaluated. This meta-analysis was based on 16 studies with 8,541 individuals. Pooled results suggested that superior calyceal access could offer fewer failed stone clearance [odds ratio (OR): 0.64, 95% confidence interval (CI), 0.47–0.88, P = 0.006] and lower additional puncture rate (OR: 0.35, 95% CI, 0.24–0.51, P < 0.001) than other calyceal access. No complication difference was found (OR: 1.10, 95% CI, 0.78–1.56, P = 0.57). Superior calyceal access could offer shorter operation time [standard mean difference (SMD): −0.57, 95% CI, −0.98 to −0.15, P = 0.007]. No hospital stay difference was found (SMD: 0.07, 95% CI, −0.09 to 0.22, P = 0.38). Large heterogeneity was detected in stone clearance comparison (I2 = 71%, P < 0.001) and operation time (I2 = 97%, P < 0.001). The stone clearance comparison also identified significant publication bias (P = 0.026). These defects weaken the credibility of the results. Superior calyceal access in PCNL may result in a higher stone clearance rate, a lower rate of subsequent punctures, and a faster operation duration with no increase in postoperative complications or hospital stay for kidney stone patients, despite the significant heterogeneity and publication bias. By conducting bigger randomized controlled studies, this discovery still has to be confirmed.