American journal of clinical and experimental urology最新文献

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of kidney tumor that has only recently been described, with less than eighty cases in the literature. This was only recognized as a specific entity in the World Health Organization 2004 classification of Renal Cell Carcinoma (RCC). MTSCCs are polymorphic renal neoplasms characterized by small, elongated tubules lined by cuboidal cells with cords of spindled cells separated by pale mucinous stroma. We report the case of a 57 year old lady who had an incidental finding of a mass in her right kidney. The radiological features were consistent with a RCC and following a multidisciplinary team discussion she underwent a laparoscopic radical nephrectomy. Macroscopic examination revealed a well circumscribed 6.5 × 6 × 6.5 cm right lower pole mass. Histologically it was composed of elongated tubules, small tubules and papillary structures with a necrotic centre. The cells demonstrated cuboidal and spindle cell morphology. Histological grade was Fuhrman grade 2. The majority of MTSCCs are indolent, and there are only two reports of distant metastases which responded favorably to adjuvant sunitinib. To date there is no international consensus on long term surveillance of these patients. Due of the favorable prognosis with this type of tumor, MTSCC must be differentiated from papillary renal cell carcinoma to avoid administration of excessive adjuvant treatment to patients.

The most common histological type of urinary bladder cancer is urothelial carcinoma (UC). Clear cell adenocarcinoma (CCA) of the urinary bladder is a rare histologic subtype of adenocarcinoma in the urinary tract. The tumor primarily affects women and has histomorphological features resembling CCA of the female genital tract (or Müllerian origin). Clear cell adenocarcinoma consists of cells with abundant clear cytoplasm, arranged in solid, glandular, or tubulocystic patterns. Patients typically present with gross hematuria, dysuria, and discharge. In this study, we report a case of a 50-year-old male, presenting with gross hematuria, which was subsequently diagnosed with CCA at our pathology department. Furthermore, we provide a short systematic review of the literature for this rare histopathological entity and a brief discussion about its morphological and immunohistochemical (IHC) characteristics.

To assess the effectiveness of a pulse duration alterable Holmium-YAG (Ho:YAG) laser on the stone-free rate (SFR) compared to a conventional pulse duration fixed laser after ureterorenoscopic lithotripsy (URSL). The medical records from patients with upper urinary tract calculi of ≥ 9 mm and < 30 mm were retrospectively investigated. URSL using a conventional Ho:YAG Laser (group C) or a pulse duration alterable Ho:YAG system (group A) was included. In total, 228 and 188 patients were enrolled in groups C and A, respectively. A 272 µm optical core bare-ended, reusable laser fiber was used, and the laser system was set to a standard 0.8 J and 10 Hz (8 W of average power) in both groups. URSL adopts active fragmentation using an extraction approach. SF was defined as the complete absence of stone fragments on computed tomography (CT) 1-2 months after URSL. Sex, BMI, stone length, stone volume, stone density, and the number of patients with positive preoperative urine cultures were not significantly different between the groups. However, age, rate of preoperative febrile urinary tract infection (fUTI), and pre-stenting were significantly higher in group A, and the operative times and incidence of postoperative fUTI were comparable. The SFRs were 71.5% and 80.3% in groups C and A, respectively (P = 0.035). Multivariate logistic regression revealed that the use of conventional laser was associated with non-SF (odds ratio [OR] 1.090, 95% confidence interval [CI] 1.01-1.18, P = 0.040). The present study revealed the superior performance of a pulse duration alterable Ho:YAG laser on the SFR after URSL compared to a conventional pulse duration fixed laser delivery system.

Background: Percutaneous nephrolithotomy (PCNL) is an effective surgery for complex kidney stones yet with inherent bleeding risks. It remains unclear whether aspirin should be discontinued prior to PCNL. We aimed to further substantiate the safety of continuing aspirin during PCNL surgery and to determine whether aspirin status affects postoperative outcomes following PCNL.

Methods: We retrospectively queried our endourology database for patients who underwent PCNL from October 2017 to December 2022 at our high-volume tertiary referral center. The three groups were based on aspirin status at the time of PCNL: no aspirin (NA), discontinued aspirin (DA), and continued aspirin (CA). Data collected included demographics, preoperative characteristics, operative parameters, pre and postoperative lab values, transfusions, and complications.

Results: A total 648 patients were divided into these study groups: 525 NA patients (81.0%), 55 DA (8.5%), and 68 CA (10.5%). The DA and CA groups were of similar comorbidities, and both were more comorbid at baseline than NA. Postoperative change in lab values and complications did not differ significantly. Rates of postoperative blood transfusion were higher in the CA and DA groups compared to NA and approached statistical significance. There were no significant differences in any postoperative outcomes between the DA and CA groups alone.

Conclusions: In patients on chronic aspirin therapy, continuing aspirin appears equally safe to discontinuing aspirin prior to PCNL. Most patients should not forego the benefits of continuous aspirin for the theoretical risk of bleeding. Patients on prolonged aspirin therapy may be more likely than those who are not on chronic aspirin therapy to require blood transfusions. However, regardless of whether aspirin use is stopped, this may be caused by patient comorbidities rather than higher rates of blood loss.

Background: Risk factors for prostate cancer include age, environment, race and ethnicity. Genetic variants in cyclic-adenosine-monophosphate-response-element-binding protein 3 regulatory factor (CREBRF) gene are frequently observed in Pacific Islanders, a population with elevated prostate cancer incidence. CREBRF has been shown to play a role in other cancers, however its function in prostate homeostasis and tumorigenesis has not been previously explored. We determined the incidence of CREBRF alterations in publicly available databases and examined the impact of CREBRF deletion on the murine prostate in order to determine whether CREBRF impacts prostate physiology or pathophysiology.

Methods: Alterations in CREBRF were identified in prostate cancer patients via in silico analysis of several publicly available datasets through cBioPortal. Male Crebrf knockout and wild-type littermate mice were generated and examined for prostate defects at 4 months of age. Immunohistochemical staining of murine prostate sections was used to determine the impact of Crebrf knockout on proliferation, apoptosis, inflammation and blood vessel density in the prostate. Serum adipokine levels were measured using a Luminex Multiplex Assay.

Results: CREBRF alterations were identified in up to 4.05% of prostate tumors and the mutations identified were categorized as likely damaging. Median survival of prostate cancer patients with genetic alterations in CREBRF was 41.23 months, compared to 131 months for patients without these changes. In the murine model, the prostates of Crebrf knockout mice had reduced epithelial proliferation and increased TUNEL⁺ apoptotic cells. Circulating adipokines PAI-1 and MCP-1 were also altered in Crebrf knockout mice compared to age-matched controls.

Conclusions: Prostate cancer patients with genetic alterations in CREBRF had a significantly decreased overall survival suggesting that wild type CREBRF may play a role in limiting prostate tumorigenesis and progression. The murine knockout model demonstrated that CREBRF could modulate proliferation and apoptosis and macrophage density in the prostate. Serum levels of adipokines PAI-1 and MCP-1 were also altered and may contribute to the phenotypic changes observed in the prostates of Crebrf knockout mice. Future studies focused on populations susceptible to CREBRF mutations and mechanistic studies will be required to fully elucidate the potential role of CREBRF in prostate tumorigenesis.

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.

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.

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.