Microbiome within Primary Tumor Tissue from Renal Cell Carcinoma May Be Associated with PD-L1 Expression of the Venous Tumor ThrombusRead the full article
Advances in Urology provides a forum for urologists, nephrologists, and basic scientists working in the field of urology. The journal publishes articles focusing on the male and female urinary tract and the male reproductive organs.
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Efficacy of Tamsulosin plus Tadalafil versus Tamsulosin as Medical Expulsive Therapy for Lower Ureteric Stones: A Randomized Controlled Trial
Introduction. Urolithiasis is one of the common disorder with which about 1/5th is found in the ureter, of which 2/3rd is seen in the lower ureter. Medical expulsive therapy is one of the routine modalities of treatment which uses various drugs acting on the ureter smooth muscle by different mechanism. We aim to compare the efficacy of combination vs. single drug. Methods. This randomized controlled trial was done in 176 consecutive patients over a period of six months (March 2019 to August 2019) in Department of Urology and Kidney Transplant Surgery, Tribhuvan University Teaching. Participants were divided into two groups (Group A, tamsulosin plus tadalafil, and Group B, tamsulosin) from computer-generated random numbers. Therapy was continued for a maximum of 3 weeks. Stone expulsion rate, time to stone expulsion, analgesic use, number of colic and emergency room visits for pain, early intervention, and adverse effects of drugs were recorded. Results. Among 176 patients who were enrolled in study, 7 were lost to follow-up, and 5 people required immediate intervention. There was a significant higher stone passage rate in group A than group B (64 vs. 50; ) and shorter expulsion time (1.66 vs. 2.32 weeks ) and less number of emergency room visits and colic episodes. No significant side effects were noted during study. Conclusion. Tamsulosin plus Tadalafil is more effective than tamsulosin with early passage of stone and decreased number of colic episodes and emergency visits without significant side effects for lower ureteric calculi of 5 mm to 10 mm.
Prospective Multicenter Open-Label One-Arm Trial Investigating a Pumpkin Seed, Isoflavonoids, and Cranberry Mix in Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia: A Pilot Study
Phytotherapy for lower urinary tract symptoms (LUTSs) due to benign prostate hyperplasia (BPH) is progressively demanded by patients and trusted by physicians. The aim was to assess the efficacy of a mix of pumpkin seed extract, soy germ isoflavonoids, and cranberry (Novex®) in the management of mild to moderate LUTS in BPH patients. Male patients aged ≥40 years, who had had mild to moderate LUTS for >6 months at screening, with no previous therapy or who are still symptomatic despite current use of alpha-blockers, were recruited. Exclusion criteria were an IPSS >19 and an age >80 years. The mixed compound was administered orally, daily, for 3 months. Patients were evaluated by means of IPSS, urological quality of life (uQoL) index, and International Index of Erectile Function (IIEF-5) at 3 visits: baseline (visit 1), 30 days (visit 2), and 90 days after treatment (visit 3). Among 163 screened patients, 128 patients (61.8 ± 9.9 years) were recruited. IPSS improved from 15 (Q1 : 12–Q3 : 17) in visit 1, to 11 (Q1 : 8–Q3 : 14) in visit 2, and to 9 (Q1 : 6–Q3 : 12) in visit 3 (). uQoL improved from 4 (3–4) in visit 1, to 3 (2–3) in visit 2, and to 2 (1–2) in visit 3 (). The patients had an IIEF-5 score of 15 (12–18.7) in visit 1, 15 (12–18) in visit 2, and 17 (13–19) in visit 3 ( visits 1 vs. 2, visits 2 vs. 3, and visits 1 vs. 3). Treating mild to moderate LUTS/BPH patients with Novex® might therefore relieve symptoms, improve the quality of life, and have a mild beneficial effect on erectile function.
Traumatic Bladder Ruptures: A Ten-Year Review at a Level 1 Trauma Center
Bladder rupture occurs in only 1.6% of blunt abdominopelvic trauma cases. Although rare, bladder rupture can result in significant morbidity if undiagnosed or inappropriately managed. AUA Urotrauma Guidelines suggest that urethral catheter drainage is a standard of care for both extraperitoneal and intraperitoneal bladder rupture regardless of the need for surgical repair. However, no specific guidance is given regarding the length of catheterization. The present study seeks to summarize contemporary management of bladder trauma at our tertiary care center, assess the impact of length of catheterization on bladder injuries and complications, and develop a protocol for management of bladder injuries from time of injury to catheter removal. A retrospective review was performed on 34,413 blunt trauma cases to identify traumatic bladder ruptures over the past 10 years (January 2008–January 2018) at our tertiary care facility. Patient data were collected including age, gender, BMI, mechanism of injury, and type of injury. The primary treatment modality (surgical repair vs. catheter drainage only), length of catheterization, and post-injury complications were also assessed. Review of our institutional trauma database identified 44 patients with bladder trauma. Mean age was 41 years, mean BMI was 24.8 kg/m2, 95% were Caucasian, and 55% were female. Motor vehicle collision (MVC) was the most common mechanism, representing 45% of total injuries. Other mechanisms included falls (20%) and all-terrain vehicle (ATV) accidents (13.6%). 31 patients had extraperitoneal injury, and 13 were intraperitoneal. Pelvic fractures were present in 93%, and 39% had additional solid organ injuries. Formal cystogram was performed in 59% on presentation, and mean time to cystogram was 4 hours. Gross hematuria was noted in 95% of cases. Operative management was performed for all intraperitoneal injuries and 35.5% of extraperitoneal cases. Bladder closure in operative cases was typically performed in 2 layers with absorbable suture in a running fashion. The intraperitoneal and extraperitoneal injuries managed operatively were compared, and length of catheterization (28 d vs. 22 d, ), time from injury to normal fluorocystogram (19.8 d vs. 20.7 d, ), and time from injury to repair (4.3 vs. 60.5 h, ) were not statistically different between cohorts. Patients whose catheter remained in place for greater than 14 days had prolonged time to initial cystogram (26.6 d vs. 11.5 d) compared with those whose foley catheter was removed within 14 days. The complication rate was 21% for catheters left more than 14 days while patients whose catheter remained less than 14 days experienced no complications. The present study provides a 10-year retrospective review characterizing the presentation, management, and follow-up of bladder trauma patients at our level 1 trauma center. Based on our findings, we have developed an institutional protocol which now includes recommendations regarding length of catheterization after traumatic bladder rupture. By providing specific guidelines for initial follow-up cystogram and foley removal, we hope to decrease patient morbidity from prolonged catheterization. Further study will seek to allow multidisciplinary trauma teams to standardize management, streamline care, and minimize complications for patients presenting with traumatic bladder injuries.
Nephrolithiasis and Polycystic Ovary Syndrome: A Case-Control Study Evaluating Testosterone and Urinary Stone Metabolic Panels
Introduction. Both elevated testosterone and polycystic ovary syndrome (PCOS) have been speculated as possible risk factors for kidney stone formation; however, the details of this potential relationship with regards to 24-hour urine metabolic panels and stone composition have not previously been characterized. Methods. A total of 74 PCOS patients were retrospectively identified and matched with a cohort of female stone formers at a 3 : 1 ratio (by age and BMI). All patients had 24-hour urinary metabolic panels and stone compositions. These groups were compared using Pearson chi-square and Student t-tests. Additionally, the PCOS group was differentiated based on free testosterone using multivariate analysis. Results. The case-control cohort showed that PCOS patients had significantly lower sodium excretion and hypernatriuria rates (28.9% vs 50.9%, ). The PCOS-testosterone cohort demonstrated that high testosterone patients had significantly higher citrate values and significantly lower odds of hypocitraturia (36.7% vs 54.2%, OR = 0.2, ). The high testosterone group also had higher sodium excretion with significantly higher odds of having hypernatriuria (40.0% vs 13.6%, OR = 13.3, ). No significant patterns were revealed based on stone composition analysis. Conclusions. Compared to healthy stone formers, PCOS patients did not demonstrate significant differences in 24-hour urine and stone composition values. Elevated free testosterone in PCOS patients has a significant association with higher urinary citrate and sodium values: findings that in and of themselves do not confirm the hypothesized increased risk of stone formation. This patient cohort may provide deeper insight into the interplay between androgens and stone formation; however, further study is needed to fully characterize the possible relationship between PCOS and stone formation.
Insights into the Regulatory Roles of E3 Ubiquitin Ligases Associated with VHL-HIF Axis in Clear Cell Renal Cell Carcinoma
Renal cell carcinoma (RCC) accounts for up to 85% to 90% of all kidney cancers. Clear cell RCC (ccRCC), the major subtype of RCC, is mainly characterized by the inactivation of the tumor suppressor gene VHL. pVHL as an E3 ubiquitin ligase targets the hydroxylated form of HIF-α for proteasomal degradation. The loss of VHL function leads to HIF-α aggregation as the main mechanism of ccRCC. Recently, the regulations of ccRCC through other E3 ubiquitin ligases are emerging. Moreover, most of them are associated with the VHL-HIF axis. In this review, we mainly focus on seven E3 ubiquitin ligases JADE1, SIAH1, CHIP, FBXW7, MDM2, SPOP, and HAF. Based on reported researches of these ligases on ccRCC, they are divided into two groups: JADE1, SIAH1, CHIP, and FBXW7 that negatively regulate the growth of ccRCC; MDM2, SPOP, and HAF that promote ccRCC progression. In addition, we further verify these possible links between these E3 ligases and VHL-HIF axis in ccRCC based on The Cancer Genome Atlas RNA-seq and Clinical data. Understanding the mechanisms by which these ligases regulate ccRCC, especially the interplay between these ligases and VHL-HIF axis may enable the development of novel therapeutic approaches for ccRCC. Overall, the present review reveals the potential mechanism by which seven ligases (JADE1, SIAH1, CHIP, FBXW7, MDM2, SPOP, and HAF) regulate ccRCC progression in detail, especially their relationship to VHL-HIF axis.
Histoprotective Effect of Essential Oil from Citrus aurantifolia in Testosterone-Induced Benign Prostatic Hyperplasia Rat
Background. Benign prostatic hyperplasia (BPH) is a common urological disorder reported among ageing men. Objective. The study assessed histoprotective effect of lime essential oil (LEO) in a rat model of testosterone-induced benign prostatic hyperplasia (BPH) and evaluated its ability to reverse testosterone-mediated changes in the testis, kidney, and liver. Materials and Methods. Adult Sprague Dawley (aged 12 weeks, 240–390 g) male rats were intramuscularly injected with testosterone enanthate (TE) (10 mg/kg) reconstituted in olive oil for ten days to establish benign prostatic hyperplasia (serum PSA level ≥ 1.24 ng/ml) in. After confirmation of BPH (sustained serum PSA level ≥ 1.24 ng/ml), rats in all groups (LEO: 30, 100, and 300 mg/kg, po, n = 6; finasteride: 15 mg/kg, po, n = 6) except model (BPH without treatment) and sham (no BPH and no treatment) groups were treated for 21 days. At the end of treatment, rats were anesthetised and blood was collected via cardiac puncture to determine serum PSA and total antioxidant capacity (TAC) levels. The prostate gland, testis, kidney, and liver were harvested, weighed, histologically processed and stained with H&E. Results. LEO- and finasteride-treated groups recorded lesser mean prostatic weights relative to their model group. Baseline mean serum PSA level of LEO- and finasteride-treated groups reduced significantly () relative to model group. Serum TAC levels were also higher in LEO- and finasteride-treated groups relative to model group. LEO-treated groups had less thickened glandular epithelium, smaller acini, fewer prostatic secretions and more fibromuscular stroma relative to model group. LEO and finasteride treatment produced improved histomorphological characteristics of testis, kidney, and liver compared to model group. Conclusion. By the current results, Citrus aurantifolia LEO may possess active agents that can be explored for translational medicine against BPH.