American journal of clinical and experimental urology最新文献

Purpose: To assess whether therapeutic and toxic effects of intravesical lidocaine are determined by coincident serum levels.

Material and methods: Published clinical trials and case studies on instilled lidocaine 1-2% that reported serum lidocaine levels were analyzed using model independent pharmacokinetic equations to compute the absorbed dose fraction (F) for linear regression with the respective dwell times.

Results: Rapid absorption of intravesical lidocaine is evinced by the serum levels of 0.16±0.3 mg/L at 5 min in bladder cancer patients coinciding with the rapid onset of pain relief (<5 min) and blood pressure drop (≥10 mm Hg) in spinal cord injured patients. Serum levels at 5 min are raised five-fold by alkalinization for a tertiary amine with pKa of 7.8 and a linear rise in F with longer dwell time (r² = 0.80; P<0.005) conforms to passive, paracellular diffusion of amphiphilic lidocaine (log P of 1.68) around umbrella cell borders with absorption rate at least five times faster than the terminal elimination rate, and therefore the delay in blood sampling after instillation is unwarranted. A rapid resolution of therapeutic and toxic effects is predicated on the extensive dilution of absorbed lidocaine with a rapid distribution half-life of 3.6 min in body weight dependent Vd - 15 times larger than blood volume, 0.13-4.5 L/kg which necessitates dose adjustment in children.

Conclusion: Whether rapid absorption of instilled lidocaine is complicated by an equally rapid and extensive dilution in body weight dependent Vd can be resolved by early blood sampling (<30 min) for: evidence-based medicine, avoidance of lidocaine toxicity in children and to educate the evolution of lidocaine solution to gel and devices.

Objective: The choice of lithotripter is an important part of planning in mini-percutaneous nephrolithotomy (mini perc) as the operating time is prolonged due to reduced sheath size and smaller working channel. Previous studies mostly reported the use of laser lithotripter for stone fragmentation while the literature on pneumatic lithotripter use in miniperc is scant.

Methods: In this study, we compared the efficacy and safety of the laser lithotripter (LL) vs pneumatic lithotripter (PL) in miniperc for small to medium-sized renal/upper ureteric stones (size: 1-2 cm). All consecutive patients who underwent miniperc from September 2020 to August 2022 were included in the study. Laser lithotripter was used in 81 patients (group LL), while pneumatic was used in 75 patients (group PL). The preoperative, operative, and postoperative findings were compared.

Results: Baseline patient characteristics (age, sex, body mass index, and co-morbid illness) and stone characteristics (size, stone number, laterality, presence of staghorn calculi, presence of hydronephrosis, Guy's stone scores) were comparable between the two groups (P>0.05). The mean operative time was comparable (P=0.38) while the mean fragmentation time was significantly higher in the PL group (35.42±6.34 vs 28.96±2.82 minutes; P<0.01). 29.3% required forceps/basket for stone removal in PL group as compared to 7.4% in LL group (P=0.02). Mean VAS (Visual Analog Scale) score on the first post-operative day, stone clearance, drop in hemoglobin, average hospital stay, stone clearance at 3 months postoperative, and complications were comparable (P>0.05).

Conclusion: Lithotripsy with pneumatic lithotripter can be used as an equally effective and safe alternative to laser lithotripter in mini-perc for treatment of small-medium sized renal/upper ureteric calculi.

During mammalian evolution, circulating levels of gonadotropins [i.e., luteinizing hormone (LH) and follicle-stimulating hormone (FSH)] acquired regulation by environmental (e.g., light, temperature, water, food, predators, etc.), and social (e.g., sound, sight, aggression, crowding, etc.) inputs that determine the level of testosterone production and secretion by the testis and systemic levels in the blood. This regulation became coordinated by interaction between the retinohypothalamic-pineal and the hypothalamic-pituitary neural axes, which resulted in androgen levels and its ligand-dependent transducing receptor being the master downstream determinant of male reproduction. A major factor in this selection of androgen levels relates to the unique danger of mammalian reproduction for survival of the individual. During mammalian evolution, breeding needed for survival of the species became episodically (i.e., seasonally) timed by androgen levels. Seasonal breeding has great reproductive advantage in restricting energy requirements for reproduction and limiting dangers associated with procreation (i.e., survival of the species) at the expense of suppression of the flight instinct (i.e., survival of the individual) to the minimal time frame of the breeding season. Human males evolved away from strict seasonal breeding by chronically maintaining androgen levels, enabling human males to reproduce year-round and worldwide, rather than "locking" them into specific indigenous breeding ranges, like other mammals. The price for the reproductive "freedom" that arises from the loss of seasonal breeding is an increased probability of developing prostate cancer as a result of chronically maintaining a hyperplastic state in the prostate. In human males, this results in the loss of episodic pruning of genetically-mutated prostate cancer precursors that normally occurs during seasonal breeding. Instead, the continuous androgen-dependent stimulation of the growth of such precursors occurs during prostate carcinogenesis. This review provides the rationale for the development of a therapeutic approach using PSA-activated prodrugs to selectively deplete prostate-specific AR protein for chemoprevention of prostate cancer.

Introduction: Various techniques have been developed for the rapid control of bleeding as a potential surgical complication. Research shows that the Surgicel has a significant effect on reducing bleeding in most surgeries; however, in our experimental observations on patients undergoing open prostatectomy, not only no significant reduction was seen in the amount of bleeding, but in some cases, Surgicel led to infection. Therefore, in this study, the effect of the Surgicel on infection and bleeding in open prostatectomy was investigated.

Materials and methods: Thirty patients undergoing open prostatectomy were randomly divided into two groups. To control bleeding after suturing the bladder neck, the Surgicel was installed in the first group, while it was not in the second group. Hemoglobin, hematocrit, PT, PTT, INR, bleeding rate, and postoperative complications were evaluated in all patients.

Results: In the studied groups, hemoglobin level and hematocrit percentage before surgery and on the first and second days after surgery, along with coagulation status, were compared in terms of PT, PTT, and INR. There were no significant differences between the studied variables and baseline variables.

Conclusion: The present study revealed that the Surgicel in open prostatectomy was ineffective in controlling bleeding and can lead to infection.

Regular consumption of cruciferous vegetables has numerous health benefits, including reduced cancer risk and improved patient outcomes. Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables with a chemoprotective role against epithelial cancers, particularly of the bladder. Epithelial cells have several functions, including secretion, absorption, filtration, and protection from environmental insults. The specialized stratified epithelium of the bladder has direct and frequent contact with carcinogenic agents, increasing the likelihood of cancer initiation at this site. Carcinogen exposure, particularly from cigarette smoke or occupational exposure to aromatic amines, are the most significant risk factors for bladder cancer due to their ability to activate inflammatory pathways, induce free radicals, and damage DNA. SFN acts as an antioxidant by activating phase II enzymes involved in carcinogen detoxification to prevent DNA damage and inhibit tumor initiation, modulates multiple signaling pathways to inhibit tumor growth and progression, and has anti-inflammatory and immune-modulating properties to help protect against cancer. Due to these chemoprotective mechanisms, SFN has been studied as both mono- and adjuvant therapy in several bladder cancer models. Here we present a review of the effects of SFN on carcinogen-induced bladder cancer to support the inclusion of cruciferous vegetables as a chemoprotective strategy.

Background: To compare the effect of botulinum toxin-A (BoNT-A) injection versus oral anticholinergic agents following transurethral resection of the prostate (TURP) in patients with benign prostatic hyperplasia (BPH) and Overactive Bladder.

Materials and methods: In this randomized clinical trial from February 2021 till May 2022 data of patients with obstructive urinary symptoms and urgency incontinence were analyzed. The intervention group consisted of 35 patients who were injected with 300 units of BoNT-A (Dysport^®) into the detrusor muscles at the same time as TURP. 38 participants in the control group were treated with solifenacin 5 mg (Urinacin^®) daily after TURP.

Results: In the evaluation of 73 included patients (mean age: 67.54±6.3), IPSS score change (first month, P=0.777; 6^th month, P=0.761) and storage irritative symptoms change score (first month, P=0.995; 6^th month, P=0.962) were decreased and Qmax was increased (first month, P=0.195; 6^th month, P=0.174) similarly in 2 groups. Lower number of patients experienced urgency incontinence during follow up time in intervention group, significantly (first month, 18 versus 5, P=0.002; 6^th month, 20 versus 6, P=0.002). PVR was also decreased more in first month and 6^th month follow up in patients of intervention group (1^th month, P=0.012; 6^th month, P=0.033).

Conclusion: Anticholinergic agents or intradetrusor BoNT-A injection would improve the storage symptoms in patients with BPH and detrusor overactivity following TURP. In contrast to IPSS score, storage irritative score and Qmax, which improve similarly in both groups, the PVR and urgency incontinence episodes will improve more in patients receive intradetrusor BoNT-A injection.

Mental illness and brain disorders such as dementia are commonly encountered in patients with cognitive impairment in urology. In this cohort study, we assessed the prevalence and outcomes of inpatient admissions for stone disease in patients with cognitive impairment. Using the National Inpatient Sample database, we identified adults (>18 years) with stone disease between 2015 and 2019. The patients were dichotomized based on the presence or absence of cognitive impairment. The groups were compared for baseline differences in inpatient admissions and hospital complications. We evaluated the independent factors associated with urinary complications in the population using multivariate logistic regression. We identified 223,072 patients with stone disease. Patients with cognitive impairment were significantly (P<0.001) older (68 vs. 62 years), female (55.7% vs. 47.4%), had government-issued insurance (77.5% vs. 64.4%), and were discharged to a nursing facility (31.7% vs. 14.2%). Patients with cognitive impairment had significantly higher rates of urinary tract infection (29.7% vs. 21.5%, P<0.001), pneumonia (5.6% vs. 4.6%, P<0.001), systemic sepsis (4.3% vs. 3.8%, P<0.001), and acute renal failure (0.9% vs. 0.7%, P = 0.008). Female sex, low income, and cognitive impairment were all independently more likely to experience a urinary complication, with significant differences (P<0.001). Patients with cognitive impairment have a higher prevalence of stone disease and urinary complications associated with inpatient admissions than the rest of the population. Health care inequities among cognitively impaired patients should be a topic of further study.

Tacrolimus is an immunosuppressant with a narrow therapeutic index and pharmacokinetic variability. This variability may be attributed to genetic variants in gene CYP3A5 associated with Tacrolimus metabolism. Studies focusing on genetic variants in the CYP3A5 gene associated with Tacrolimus metabolism have been published, a meta-analysis of these published articles may provide a direction that can change the future research and clinical management of renal transplant patients. In this systematic review and meta-analysis, we have reviewed and analyzed the studies and clinical trials conducted to determine the association between genetic variants of CYP3A5 and Tacrolimus metabolism from the PubMed database and clinical trials (www.clinicaltrials.gov). This meta-analysis also assessed the correlation of CYP3A5 genotype (rs776746) with concentration/dose (C_o/D) of Tacrolimus in renal transplant patients. The 59 published articles on genetic association of the CYP3A5 on Tacrolimus doses were reviewed for this systematic review. Meta-analysis showed that the Tacrolimus C_o/D ratio is significantly lower in the CYP3A5 expressor group as compared with non-expressor in Asian, European as well as in mixed populations at any post-transplant period (P<0.0001). Our study further confirmed that the CYP3A5 variant (rs776746) is clinically relevant for the dose determination of Tacrolimus. Variations in Tacrolimus C_o/D have been found to be significantly linked to the patient's CYP3A5 genetic variant (rs776746). The addition of other genetic variants involved in the pharmacokinetic of Tacrolimus may determine efficient regimen for drug dose. Our meta-analysis confirmed that the CYP3A5 genetic variant (rs776746) analysis is relevant in personalizing the Tacrolimus dose determination in renal transplant patients.

Retinoblastoma transcriptional corepressor 1 (RB1) and tumor protein p53 (TP53) are well-known tumor suppressor genes; their alterations are associated with poor prognosis in human malignancies and quite rare in locally recurrent cases. The patient was a 58-year-old man who was diagnosed with cT1cN0M0 prostate cancer with Gleason score of 3+3=6 and underwent brachytherapy as the initial treatment. Local recurrence was detected in the left lobe of the prostate 154 months later and whole-exome sequencing that was performed at the request of the patient revealed RB1 loss-of-heterozygosity and TP53 p.I162Rfs*27 mutations. He underwent salvage focal brachytherapy with ¹²⁵I seeds and serum prostate-specific antigen levels has been stabilized without any genitourinary or gastrointestinal toxicity.

Background: RAKT is a relatively newer approach for kidney transplant and has to be proven against the established approach, OKT. RAKT may be beneficial in obese patients as described in literature. Hence, we compared pre-, intra- and postoperative parameters with one year follow-up of both approaches by propensity matching similar characteristics patients.

Methods: Data of 28 OKT and 28 RAKT propensity matched patients was collected during 2014 to 2022 through the institutional transplant registry. OKT and RAKT patients were propensity matched for confounding factors like donor age, eGFR, side along with recipient age, BMI and comorbidities. All graft kidneys were harvested laparoscopically.

Results: Both the groups were comparable in terms of recipient age and BMI, donor age, creatinine, BMI, eGFR and comorbidities. Total ischemia time (P<0.001) and postoperative day (POD) 1 creatinine (P<0.001) was significantly more in RAKT. However, postoperative 1 month (P=0.12), 3 months (P=0.60) and 1 year (P=0.10) creatinine was comparable in both approaches. Postoperative complications (P=0.90) including hemoglobin drop (P=0.72) were comparable in both the groups. The days to half the creatinine from preoperative values was significantly less in OKT group (P=0.009). Serum Tacrolimus levels at day 3 (P=0.08) and day 7 (P=0.112) were also comparable in both the groups. Graft survival was 78.5% in OKT group and 82.14% in RAKT group with median follow-up of 60 months in both the groups.

Conclusion: In this comprehensive propensity matched analysis of RAKT with OKT, we conclude that RAKT has similar outcomes as OKT at 1 year and 5 years follow-up. CIT, TIT, time to half creatinine and POD 1 creatinine values were higher in RAKT group, but eventually have comparable outcomes at further follow-up. Thus, RAKT, a novel approach is non-inferior to established OKT approach. However, further larger trials are required.