Journal Club    2024.02.26 (1402.12.07)

1- Dr. Mohamadi: Pyuria as an independent predictor of intravesical recurrence after radical nephroureterectomy in patients with upper tract urothelial carcinoma

https://doi.org/10.4111/icu.20230066

About one-third of patients who undergo radical nephroureterectomy (RNUx) for upper tract urothelial carcinoma (UTUC) experience intravesical recurrence (IVR). This study investigated whether pyuria is a feasible predictor of IVR after RNUx in patients with UTUC. Seven hundred forty-three patients with UTUC who underwent RNUx at a single institute were analyzed in this study. The participants were divided into two groups: those without pyuria (non-pyuria) and those with pyuria. Kaplan–Meier survival analysis was performed, and p-values were assessed using the log-rank test. Cox regression analyses were performed to identify the independent predictors of survival. The pyuria group had a shorter IVR-free survival period (p=0.009). The five-year IVR-free survival rate was 60.0% in the non-pyuria group vs. 49.7% in the pyuria group according to the Kaplan-Meier survival analysis. After the multivariate Cox regression analysis, pyuria (hazard ratio [HR]=1.368; p=0.041), a concurrent bladder tumor (HR=1.757; p=0.005), preoperative ureteroscopy (HR=1.476; p=0.013), laparoscopic surgery (HR=0.682; p=0.048), tumor multiplicity (HR=1.855; p=0.007), and a larger tumor (HR=1.041; p=0.050) were predictors of risk for IVR. There was no association between pyuria and recurrence-free survival (p=0.057) or cancer-specific survival (p=0.519) in the Kaplan–Meier survival analysis. This study concluded that pyuria was an independent predictor of IVR in patients with UTUC after RNUx.Journal Club

2-Dr.Najarzadegan: Prognostic and predictive value of tertiary lymphoid structures in TURBT materials; Should it be seated in routine pathological examination and can it be used in deciding on the treatment method?

https://doi.org/10.21203/rs.3.rs-3962802/v2

This study aims to reveal the importance of tertiary lymphoid structures (TLS) in TURBT materials with a practical and applicable method in which the effect of a certain threshold value on survival and treatment response can be implicated. TURBT materials that had not previously received any treatment (chemotherapy, radiotherapy, or immunotherapy) and were diagnosed for the first time at Mardin Training and Research Hospital between 2014 and 2022 were included in the study. The maximum number of TLS per 4x magnification field (Field diameter: 4,5 mm) was recorded.Grouping and statistical analysis of the TLS number were performed using threshold values of “≥1”, “≥2” and “≥3”. TLSs were more frequently found in high-grade tumors (p=0,008) and showed a strong association with stage progression (p<0,001). It was also significantly associated with many adverse histopathological parameters. Conversely,high TLS (≥1, ≥2, and ≥3) appeared to be associated with fewer recurrences (p=0,032, p=0,001, and p=0,018, respectively), and cases with higher TLS showed longer recurrence-free survival (p=0,089, p=0,023, p=0,037, respectively). TLS≥3 was found to be an independent parameter associated with favoarable RFS (p=0,019, HR=0,401) and multifocality was found to be an independent risk factor for RFS (p=0,023, HR=2,302). This study is the first to demonstrate the relationship between the presence and specific thresholds of TLS in TURBT materials with prognostic parameters. Including this information in the routine pathological examination of TURBT materials will allow a more accurate approach to treatment and follow-up, especially in patients with NMIBC.Journal Club

3-Alphil: Ureteral stricture formation after endoscopic removal of obstructing stones: could it be predicted with well-assessed radiological parameters?

https://link.springer.com/article/10.1007/s00240-024-01530-1

The possible role of well-assessed radiological parameters in the prediction of ureteral stricture formation in cases with impacted obstructive ureteral calculi has been evaluated. 46 adult patients with or without ureteral stricture formation after ureteroscopic stone management were included. In addition to stone size and some certain radiological parameters including ureteral wall thickness (UWT) of the involved ureter at the impacted stone site was also measured and noted on computed tomography (CT) images. Parameters were evaluated in two subgroups of cases, namely: Group 1: patients in whom a ureteral stricture formed after endoscopic stone removal and Group 2: patients normal ureteral anatomy without any stricture formation. The possible relationship between the UWT values and degree of hydronephrosis (HN) with subsequent stricture formation was comparatively evaluated. All of the stones were proximal ureteral calculi in both groups. Both the degree of HN and proximal ureteral diameter (PUD) parenchymal was higher in cases with stricture formation. In addition, mean parenchymal thickness was lower and mean values of UWT measurements at the stone site were 3.70 ± 0.97 mm and 2.17 ± 0.26 mm in Groups 1 and 2, respectively. A cutoff value 2.49 mm for UWT was found to be highly predictive for stricture formation. UWT value calculated at the obstructing stone site was found to be predictive enough for the likelihood of ureteral stricture formation with high sensitivity and specificity . This evaluation along with some other radiological parameters may enable the urologists to follow such cases on this aspect with necessary measures taken.Journal Club

4- Dr.Ghiasi: Low Immunogenicity of Intravesical Phage Therapy for Urogenitary Tract Infections

https://doi.org/10.3390/antibiotics10060627

Patients with chronic urinary and urogenital multidrug resistant bacterial infections received phage therapy (PT) using intravesical or intravesical and intravaginal phage administration. A single course of PT did not induce significant serum antibody responses against administered phage. Whilst the second cycle of PT caused a significant increase in antibody levels, they nevertheless remained quite low. These data combined with good therapy results achieved in some patients suggest that this mode of PT may be an efficient means of therapy for urogenital infections and a reliable model for a clinical trial of PT.Journal Club

5-Chivaei: Comparison of Thulium Fiber Laser versus Holmium laser in ureteroscopic lithotripsy: a Meta-analysis and systematic review

https://link.springer.com/article/10.1186/s12894-024-01419-6

To compare the efficacy and safety of thulium fiber laser (TFL) to holmium: YAG (Ho: YAG) laser in ureteroscopic lithotripsy for urolithiasis. PubMed, Web of Science, Embase, CENTRAL, SinoMed, CNKI database, VIP and Wanfang Database were systematically searched for all relevant clinical trials until September 2023. References were explored to identify the relevant articles. Meta-analysis was carried out for the retrieved studies using RevMan5.4.1 software, and the risk ratio, mean difference and 95% confidence interval were expressed. Statistical significance was set at p < 0.05. The main outcomes of this meta-analysis were stone-free rate (SFR), perioperative outcomes and intraoperative or postoperative complications. Thirteen studies, including 1394 patients, were included. According to the results of pooled analysis, TFL was associated with significantly higher stone-free rate (SFR) [0.52, 95% CI (0.32, 0.85), P = 0.009], shorter operation time [-5.47, 95% CI (-8.86, -2.08), P = 0.002], and less stone migration [0.17, 95% CI (0.06, 0.50), P = 0.001]. However, there was no significant difference in terms of the laser time, duration of hospital stay, drop of hemoglobin level, total energy, postoperative ureteral stenting, the incidence of intraoperative complications or postoperative complications between TFL and Ho: YAGs. The findings of this study demonstrated several advantages of TFL in terms of higher SFR, shorter operative time and less stone migration.Journal Club

6- Dr.Beiranvand: Role of heat shock protein 70 in silibinin-induced apoptosis in bladder cancer

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10751677/

Hsp70 (heat shock protein 70) plays critical roles in cancer cell proliferation and apoptosis. Recently, accumulating evidences have demonstrated the cancer promoting effects of Hsp70 in bladder cancer. The development of novel therapeutic approaches targeting Hsp70 thus received great attention from researchers. In this study, we demonstrated that silibinin, a natural polyphenolic flavonoid isolated from the milk thistle, targeted Hsp70 by inhibiting its transcription in bladder cancer cells. We also demonstrated that knockdown of endogenous Hsp70 enhanced silibinin-induced apoptosis, while overexpression of exogenous Hsp70 could partially reverse the effects of silibinin-induced cell apoptosis. Furthermore, we found that silibinin could activate HSF1/Hsp70-regulated mitochondrial apoptotic pathway. Mechanically, silibinin inhibited the interaction between Apaf-1 and Hsp70, thus increasing the recruitment of pro caspase-9. Results from in vivo study demonstrated that silibinin suppressed the growth of bladder cancer xenografts, which was accompanied with the activation of caspase-3 and downregulation of HSF1 and Hsp70. Taken together, our data indicates that silibinin induces mitochondrial apoptosis via inhibiting HSF1/Hsp70 pathway and also suggests the therapeutic potential of silibinin in the treatment of bladder cancer.Journal Club

7-Zemanati: Genetic testing in children with nephrolithiasis and nephrocalcinosis

https://link.springer.com/article/10.1007/s00467-023-05879-0

Diagnosing genetic kidney disease has become more accessible with low-cost, rapid genetic testing. The study objectives were to determine genetic testing diagnostic yield and examine predictors of genetic diagnosis in children with nephrolithiasis/nephrocalcinosis (NL/NC). This retrospective multicenter cross-sectional study was conducted on children ≤ 21 years old with NL/NC from pediatric nephrology/urology centers that underwent the Invitae Nephrolithiasis Panel 1/1/2019–9/30/2021. The diagnostic yield of the genetic panel was calculated. Bivariate and multiple logistic regression were performed to assess for predictors of positive genetic testing. One hundred and thirteen children (83 NL, 30 NC) from 7 centers were included. Genetic testing was positive in 32% overall (29% NL, 40% NC) with definite diagnoses (had pathogenic variants alone) made in 11.5%, probable diagnoses (carried a combination of pathogenic variants and variants of uncertain significance (VUS) in the same gene) made in 5.4%, and possible diagnoses (had VUS alone) made in 15.0%. Variants were found in 28 genes (most commonly HOGA1 in NL, SLC34A3 in NC) and 20 different conditions were identified. Compared to NL, those with NC were younger and had a higher proportion with developmental delay, hypercalcemia, low serum bicarbonate, hypophosphatemia, and chronic kidney disease. In multivariate analysis, low serum bicarbonate was associated with increased odds of genetic diagnosis (β 2.2, OR 8.7, 95% CI 1.4–54.7, p = 0.02). Genetic testing was high-yield with definite, probable, or possible explanatory variants found in up to one-third of children with NL/NC and shows promise to improve clinical practice.

8- Dr.Karimian: Percutaneous nephrolithotomy non-papillary puncture trends. A review of the literatureTendencias de punción extrapapilar en nefrolitotomía percutánea. Revisión de la literatura

https://doi.org/10.1016/j.acuroe.2023.06.003

Percutaneous nephrolithotomy (PCNL) is the gold standard of treatment for large renal calculi. Papillary puncture is the mainstay of treatment for large renal calculi, but the non-papillary has been introduced and gained some interest. The aim of this study is the investigation of trends of non-papillary access for PCNL over the years. A review of the literature took place and 13 publications were included in the study. Two experimental studies investigating the feasibility of non-papillary access were found. Five cohort prospective and 2 retrospective studies for non-papillary access and 4 comparative studies between papillary and non-papillary access were included. Non papillary access is a technique that has been proved as a safe and efficient solution that keeps up with the latest endoscopic trends. A wider use of this method could be expected in the future.