Urology research center journal club: articles presentation2024.02.19 (1402.11.30)

Journal Club 2024.02.19 (1402.11.30)

1-Dr. Mohamadi: Predictors of acute kidney injury after percutaneous nephrolithotomy in adult patients: prospective observational study

https://link.springer.com/article/10.1007/s11255-024-03960-7

To assess the frequency and the predictive factors of Acute Kidney injury (AKI) in patients undergoing percutaneous nephrolithotomy (PNL). A prospective observational work. Demographic, preoperative laboratory data, stone characteristics, and intraoperative and postoperative data were gathered. Perioperative AKI had been defined as an elevation in serum creatinine by ≥ 0.3 mg/dl within 48 h, or ≥ 1.5 times baseline, or urine volume less than 0.5 ml/ kg/hour for 6 hours. A multivariate logistic regression analysis was performed to determine the predictive factors of AKI. ROC curves were utilized to determine the cutoff values of the risk variables. P-values were deemed statistically significant when they were less than 0.05. A total of 418 participants had been involved. The frequency of AKI was 13.9, and 17.2% of patients with AKI developed CKD. The risk factors were age > 46.5 years, smoking, BMI > 28.5 kg/m2, hypertension, diabetes, utilization of angiotensin-converting enzyme inhibitors (ACEI), haemoglobin < 10.8 gm/dl, baseline creatinine > 1.41 mg/dl, eGFR < 65.2 ml/min./1.73 m2, serum uric acid > 5.2 mg/dl, stone volume > 1748 mm3, large tract size, long operative time, and intra-operative bleeding. Patients with AKI had a notably extended duration of hospitalization (3.2 days ± 0.45 vs 2.1 ± 0.42, p < 0.001). Perioperative AKI occurred in 13.9% of individuals undergoing PNL. Identification and optimization of the risk factors and meticulous technique during PNL procedures should be attempted to decrease the risk of AKI.

2-Dr.Najarzadegan: Serum Filamin A is a prognostic biomarker for screening benign prostatic hyperplasia vs prostate cancer in Caucasian and African American men

https://doi.org/10.1158/1538-7445.AM2023-2196

Prostate cancer represents a significant health risk to aging men, in which diagnostic challenges pose major issues with identification of indolent and or aggressive cancers. Prostate cancer screening is driven by prostate specific antigen (PSA), however, PSA’s screening utility is diminished in men with benign prostatic hyperplasia (BPH) due to an enlarged prostate and elevated PSA, triggering unnecessary biopsies in men with this condition. Thus, there is a critical unmet medical need to identify a marker for men with these conditions. Moreover, it is crucial to test any novel biomarker in populations of different ancestry (especially African American men who have higher prostate cancer risk) to ensure results apply regardless of race. To this extent, we recently identified a cleaved fragment of Filamin A (FLNA) protein (as measured by IP-MRM mass spectrometry assessment) as a novel biomarker for stratifying BPH from prostate cancer and subsequently evaluated its utility in Caucasian and African American patients. The men had a negative digital rectal examination (DRE), PSA between 4-10 ng/ml and all underwent prostate biopsy. In African American (AA) men, FLNA expression exhibited diagnostic utility for stratifying BPH from all prostate cancer patients (0.72 AUC, 0.82 PPV, 0.76 NPV, 14.2 OR, P Value – 1.5 e-08 in 48 BPH and 139 PCa AA men) and outperformed PSA (0.54 AUC, 0.75 PPV, 0.28 NPV, 1.1 OR, P Value 0.78). In addition, FLNA could stratify BPH from Gleason 7-10 prostate cancers (0.71 AUC, 0.66 PPV, 0.86 NPV, 12.2 OR, P Value 1.7 e-05 in 48 BPH and 60 PCa AA men) and again outperformed PSA (0.5 AUC, 0.58 PPV, 0.62 NPV, 2.18 OR, P Value 0.24). In Caucasian American (CA) men, FLNA expression exhibited diagnostic utility for stratifying BPH from all prostate cancer patients (0.68 AUC, 0.68 PPV, 0.73 NPV, 5.6 OR, P Value 1.6 e-12 in 191 BPH and 281 PCa CA men) and outperformed PSA (0.56 AUC, 0.58 PPV, 0.28 NPV, 0.55 OR, P Value 0.13). FLNA could also stratify BPH from Gleason 7-10 prostate cancers (0.74 AUC, 0.46 PPV, 0.96 NPV, 19.4 OR, P Value 1.6 e-12 in 119 BPH and 109 PCa CA men) and again outperformed PSA (0.46 AUC, 0.35 PPV, 0.38 NPV, 0.32 OR, P Value 0.03). Previously we showed FLNA along with prostate volume had superior performance over PSA in identifying patients with prostate cancer (Kiebish et al Scientific Reports, 2021 Jul 23, 11(1)). Herein, we refined our analysis and establish FLNA alone as a serum biomarker for stratifying men with BPH vs prostate cancer as well as those with high Gleason prostate cancers compared to the current diagnostic paradigm of using PSA. This simplified approach demonstrates clinical actionability as a test with utility in AA and CA men and represents a significant opportunity to decrease the need for unnecessary biopsies for prostate cancer diagnosis. A clinical test is being developed to address this important medical need.

3-Dr.Alphil: Correlation between metabolic syndrome and periurethral prostatic fibrosis: results of a prospective study

https://link.springer.com/article/10.1186/s12894-024-01413-y

Prostatic fibrosis, characterized by the accumulation of myofibroblasts and collagen deposition, is closely associated with LUTS and may lead to mechanical obstruction of the urethra. Additionally, Metabolic Syndrome (MetS), characterized by central obesity, high blood sugar, lipid metabolism disorders, and hypertension, is increasingly recognized as a proinflammatory condition linked to prostate inflammation. Clinical data from 108 subjects who underwent transurethral resection of the prostate or bipolar plasmakinetic enucleation of the prostate were prospectively collected between June 2021 and August 2022. Patients were divided in two groups according to whether or not they had a diagnosis of MetS. Specimens were stained with Masson trichrome and the periurethral prostatic fibrosis extent was evaluated using quantitative morphometry. Forty-three patients (39.8%) were diagnosed with MetS. Patients with MetS showed a significantly greater extent of prostatic fibrosis than the others (68.1 ± 17.1% vs. 42.5 ± 18.2%, P < 0.001), and there was a positive correlation between the number of positive MetS parameters and the extent of prostatic fibrosis (R2 = 0.4436, P < 0.001). Multivariate regression analysis revealed that central obesity (B = 2.941, 95% confidence interval, 1.700–3.283), elevated fasting glucose (B = 1.036, 95% confidence interval, 0.293–1.780), reduced HDL cholesterol (B = 0.910, 95% confidence interval, 0.183–1.636) and elevated triglycerides (B = 1.666, 95% confidence interval, 0.824–2.508) were positively correlated to prostatic fibrosis. Elevated blood pressure, however, was unrelated to prostatic fibrosis (B = 0.009, 95% confidence interval, -0.664–0.683). The present findings suggest that prostatic fibrosis is positively correlated with MetS and its components including central obesity, elevated fasting glucose, reduced high density lipoprotein cholesterol and elevated triglycerides

4-Dr.Ghiasi: Risk Factors for Postpartum Stress Urinary Incontinence: a Systematic Review and Meta-analysis

https://link.springer.com/article/10.1007/s43032-020-00254-y

Stress urinary incontinence (SUI) is a distressing symptom affecting females globally and is one of the most common complications of delivery. The etiology of female SUI is multifactorial, and the trauma caused by delivery is one of the most important risk factors for SUI. We performed a meta-analysis to determine the relationship between these various factors and postpartum SUI. We searched PubMed, Embase, Web of Science, and the Cochrane Library until January 2019 using appropriate keywords and extracted 46 eligible studies that included 73,010 participants. The study protocol was registered with PROSPERO (No. CRD42020150094). The pooled results indicated that 12 risk factors, including vaginal delivery (OR 2.08, 95% CI 1.72–2.52), advanced age at gestation (OR 1.06, 95% CI 1.04–1.08), advanced maternal BMI (OR 1.04, 95% CI 1.03–1.06), excess weight gain during pregnancy (OR 1.13, 95% CI 1.00–1.26), advanced current BMI (OR 1.32, 95% CI 1.02–1.70), diabetes (OR 1.91, 95% CI 1.53–2.38), episiotomy (OR 1.76, 95% CI 1.06–2.94), forceps delivery (OR 2.69, 95% CI 1.25–5.76), gestational UI (OR 5.04, 95% CI 2.07–12.28), gestational SUI (OR 4.28, 95% CI 2.61–7.01), prenatal UI (OR 8.54, 95% CI 3.52–20.70), and early postpartum UI (OR 3.52, 95% CI 1.61–7.69), were associated with postpartum SUI. The findings of this analysis could serve to generate risk prediction models and provide a basis for developing treatment strategies for patients with postpartum SUI.

5-Dr.Chivaei: The relationship between biochemical recurrence and number of lymph nodes removed during surgery for localized prostate cancer

https://link.springer.com/article/10.1186/s12894-023-01228-3

To assess whether completeness of pelvic lymph node dissection (PLND) as measured by lymph node yield reduces biochemical recurrence (BCR) in men undergoing radical prostatectomy (RP) for prostate cancer (PCa), stratified according to Briganti nomogram-derived risk (≥5% vs. < 5%) of lymph node invasion (LNI). Retrospective study of 3724 men who underwent RP between January 1995 and January 2015 from our prospectively collected institutional database. All men included had minimum five years follow-up and were not given androgen deprivation therapy or radiotherapy prior to BCR. Primary endpoint was time to BCR as defined by PSA > 0.2ng/ml. Patients were analysed according to Briganti Nomogram derived risk of ‘low-risk’ (< 5%) vs. ‘high-risk’ (≥ 5%). Extent of PLND was analysed using number of nodes yielded at dissection as a continuous variable as well as a categorical variable: Group 1 (limited, 1–4 nodes), Group 2 (intermediate, 5–8 nodes) and Group 3(extensive, ≥9 nodes). Median follow-up in the overall cohort was 79.7 months and 65% of the total cohort underwent PLND. There were 2402 patients with Briganti risk of LNI < 5% and 1322 with a Briganti risk of LNI ≥5%. At multivariate analysis, only PSA (HR1.01, p < 0.001), extracapsular extension at RP (HR 1.86, p < 0.001), positive surgical margin (HR 1.61, p < 0.001) and positive lymph node on pathology (HR 1.52, p = 0.02) were independently associated with BCR. In the high-risk group, increased nodal yield at PLND was associated with red (HR 0.97, 95%CI 0.95-1.00 p = 0.05, Cochran Mantel Haenszel test, p < 0.05: respectively). In the low-risk group increased number of nodes at PLND did not reduce risk of BCR. In this study of extent of PLND at RP, higher nodal yield did not reduce risk of BCR in low-risk men (Briganti risk < 5%), however there was a weak benefit in terms of reduced long-term risk of BCR in high-risk men (Briganti risk ≥5%).

6-Dr.Beiranvand: Sea Cucumber Derived Triterpenoid Glycoside Frondoside A: A Potential Anti-Bladder Cancer Drug

https://doi.org/10.3390/nu15020378

Bladder cancer is a highly recurrent disease and a common cause of cancer-related deaths worldwide. Despite recent developments in diagnosis and therapy, the clinical outcome of bladder cancer remains poor; therefore, novel anti-bladder cancer drugs are urgently needed. Natural bioactive substances extracted from marine organisms such as sea cucumbers, scallops, and sea urchins are believed to have anti-cancer activity with high effectiveness and less toxicity. Frondoside A is a triterpenoid glycoside isolated from sea cucumber, Cucumaria frondosa. It has been demonstrated that Frondoside A exhibits anti-proliferative, anti-invasive, anti-angiogenic, anti-cancer, and potent immunomodulatory effects. In addition, CpG oligodeoxynucleotide (CpG-ODN) has also been shown to have potent anti-cancer effects in various tumors models, such as liver cancer, breast cancer, and bladder cancer. However, very few studies have investigated the effectiveness of Frondoside A against bladder cancer alone or in combination with CpG-ODN. In this study, we first investigated the individual effects of both Frondoside A and CpG-ODN and subsequently studied their combined effects on human bladder cancer cell viability, migration, apoptosis, and cell cycle in vitro, and on tumor growth in nude mice using human bladder cancer cell line UM-UC-3. To interrogate possible synergistic effects, combinations of different concentrations of the two drugs were used. Our data showed that Frondoside A decreased the viability of bladder cancer cells UM-UC-3 in a concentration-dependent manner, and its inhibitory effect on cell viability (2.5 μM) was superior to EPI (10 μM). We also showed that Frondoside A inhibited UM-UC-3 cell migration, affected the distribution of cell cycle and induced cell apoptosis in concentration-dependent manners, which effectively increased the sub-G1 (apoptotic) cell fraction. In addition, we also demonstrated that immunomodulator CpG-ODN could synergistically potentiate the inhibitory effects of Frondoside A on the proliferation and migration of human bladder cancer cell line UM-UC-3. In in vivo experiments, Frondoside A (800 μg/kg/day i.p. for 14 days) alone and in combination with CpG-ODN (1 mg/kg/dose i.p.) significantly decreased the growth of UM-UC-3 tumor xenografts, without any significant toxic side-effects; however, the chemotherapeutic agent EPI caused weight loss in nude mice. Taken together, these findings indicated that Frondoside A in combination with CpG-ODN is a promising therapeutic strategy for bladder cancecance.

Dr.Zemanati: Association between urinary phthalate metabolites and nephrolithiasis in adults: A cross-sectional analysis with NHANES 2007–2018

https://doi.org/10.1016/j.chemosphere.2023.139436

Nephrolithiasis is highly prevalent and brings health and economic burdens to patients. The augmentation of nephrolithiasis may be associated with exposure to phthalate metabolites. However, few studies investigated the effect of various phthalates exposure on nephrolithiasis. We analyzed data from 7139 participants aged 20 years or above from the National Health and Nutrition Examination Survey (NHANES) 2007–2018. Serum calcium level-stratified univariate and multivariate linear regression analyses were performed to explore the relationship between urinary phthalate metabolites and nephrolithiasis. As a result, the prevalence of nephrolithiasis was approximately 9.96%. After adjusting for confounding factors, associations were found between serum calcium concentration with monoethyl phthalate (P = 0.012) and mono-isobutyl phthalate (P = 0.003) compared with tertile 1 (T1). In adjusted analysis, nephrolithiasis was positively associated with middle and high tertiles of mono benzyl phthalate (P < 0.05) compare with low tertile group. Furthermore, high-level exposure to mono-isobutyl phthalate had a similar positive association with nephrolithiasis (P = 0.028). Our findings provide evidence that exposure to certain phthalate metabolites (i.e. MiBP and MBzP) may be associated with a high risk of nephrolithiasis depending on serum calcium level.

Dr.Karimian: Innovations in Kidney Stone Removal

https://www.tandfonline.com/doi/abs/10.2147/RRU.S386844

Urolithiasis is a common clinical condition, and surgical treatment is performed with different minimally invasive procedures, such as ureteroscopy, shockwave lithotripsy and percutaneous nephrolithotomy. Although the transition from open surgery to endourological procedures to treat this condition has been a paradigm shift, ongoing technological advancements have permitted further improvement of clinical outcomes with the development of modern equipment. Such innovations in kidney stone removal are new lasers, modern ureteroscopes, development of applications and training systems utilizing three-dimensional models, artificial intelligence and virtual reality, implementation of robotic systems, sheaths connected to vacuum devices and new types of lithotripters. Innovations in kidney stone removal have led to an exciting new era of endourological options for patients and clinicians alike.