Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04563936.

PLAU contributes to the development of cholangiocarcinoma via activating NF-κB signaling pathway.

Cholangiocarcinoma (CCA) is a type of epithelial cancer with poor outcomes and late diagnosis. Accumulating evidence has demonstrated the promoting role of plasminogen activator, urokinase (PLAU) in several tumor types, while its function in CCA is largely unknown. The expression of PLAU in CCA was determined by data from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database and further confirmed in human tissues using immunohistochemical (IHC) staining. Moreover, PLAU-silencing CCA cell models were constructed for subsequent functional assays in vitro and in vivo. PLAU expression in CCA was significantly higher than that in normal tissues. High PLAU expression was positively correlated with poor patients' survival. PLAU knockdown remarkably suppressed proliferation and migration of CCA cells, whereas enhanced apoptosis. Consistently, tumor growth in mice injected with PLAU-silencing CCA cells was also impaired. Furthermore, we revealed that the activation of NF-κB signaling was required for PLAU-induced malignant phenotypes of CCA cells. Inhibiting the high expression of PLAU in CCA may be a potential entry point for targeted therapy in CCA patient.

Primary Renal Malignant Fibrous Histiocytoma in an End-Stage Renal Disease Patient.

Besides renal cell carcinoma with increased risk reported in the dialysis population, other unusual types of renal tumors should also be considered. However, to the best of our knowledge, renal sarcomas have never been reported among end-stage renal disease patients undergoing dialysis in the literature. In this study, we present the first case of a primary renal malignant fibrous histiocytoma (MFH, also called undifferentiated pleomorphic sarcoma) in a 41-year-old woman with end-stage renal disease.

Development and validation of a nomogram to predict the prognosis of patients with squamous cell carcinoma of the bladder.

BACKGROUND: The present study aimed to develop and validate a nomogram based on expanded TNM staging to predict the prognosis for patients with squamous cell carcinoma of the bladder (SCCB). METHODS: A total of 595 eligible patients with SCCB identified in the Surveillance, Epidemiology, and End Results (SEER) dataset were randomly divided into training set (n = 416) and validation set (n = 179). The likelihood ratio test was used to select potentially relevant factors for developing the nomogram. The performance of the nomogram was validated on the training and validation sets using a C-index with 95% confidence interval (95% CI) and calibration curve, and was further compared with TNM staging system. RESULTS: The nomogram included six factors: age, T stage, N stage, M stage, the method of surgery and tumor size. The C-indexes of the nomogram were 0.768 (0.741-0.795) and 0.717 (0.671-0.763) in the training and validation sets, respectively, which were higher than the TNM staging system with C-indexes of 0.580 (0.543-0.617) and 0.540 (0.484-0.596) in the training and validation sets, respectively. Furthermore, the decision curve analysis (DCA) proved that the nomogram provided superior clinical effectiveness. CONCLUSIONS: We developed a nomogram that help predict individualized prognosis for patients with SCCB.

HSDL2 Promotes Bladder Cancer Growth In Vitro and In Vivo.

Bladder cancer is a common malignant urinary tumor, and patients with bladder cancer have poor prognosis. Abnormal lipid metabolism in peroxisomes is involved in tumor progression. Hydroxysteroid dehydrogenase-like 2 (HSDL2) localized in peroxisomes regulates fatty acid synthesis. In the present study, we reported that HSDL2 was upregulated in two human bladder cancer cell lines 5637 and T24 compared to normal human urothelial cells. Furthermore, lentiviral-mediated HSDL2 knockdown inhibited the proliferation and colony formation while promoted the apoptosis of human bladder cancer T24 cells in vitro. In nude mice HSDL2 knockdown inhibited the growth of T24 derived xenografts in vivo. In conclusion, our results suggest that HSDL2 plays an oncogenic role in bladder cancer and might serve as a potential target for bladder cancer therapy.

Primary adenocarcinoma of the renal pelvis, ureter and the urinary bladder: A case report and review of the literature.

Primary adenocarcinoma is a rare type of urological neoplasm. The present study reports the case of a 55-year-old man with multifocal adenocarcinoma of the renal pelvis, ureter and urinary bladder that occurred in association with a large cystic calculus and perinephric abscess. The patient had suffered from gross hematuria for 2 years and right flank pain for 2 months. Following a series of investigations, a large cystic calculus with multiple tumors in the renal pelvis and ureter was identified. Multifocal tumors and a large calculus were located in the bladder using a cystoscope. The pathological report of 3 individual biopsies revealed a moderately differentiated tubular adenocarcinoma. Right nephrectomy, ureterectomy, radical cystectomy and left ureterocutaneostomy were performed. The pathological investigation revealed a moderately differentiated adenocarcinoma of the renal pelvis, ureter and urinary bladder. No additional treatment was administered and the patient remains alive at follow-up without disease recurrence or metastasis. Although uncommon, the development of a tumor is possible in patients that possess long-standing urolithiasis, particularly when accompanied by hydronephrosis or infection.

Safety and efficacy of a novel disposable circumcision device: a pilot randomized controlled clinical trial at 2 centers.

BACKGROUND: We evaluated the safety and efficacy of a novel disposable male circumcision (MC) device developed by Jiangxi-Yuansheng-Langhe Medical Instrument Co., Ltd. MATERIAL AND METHODS: Adult male patients (n=120; mean age, 26.6 years) with redundant foreskin and/or phimosis were included in a randomized, multicenter pilot clinical trial from October 2011 to February 2012. Patients were divided into 2 groups and subjected to MC with a novel disposable device (Device Group) (n=60) or to conventional dissection technique (CDT) (Control Group) (n=60). Intraoperative bleeding, surgery duration, pain, healing, and satisfaction with penis appearance were assessed. Adverse events (AEs) were noted. RESULTS: Intraoperative bleeding volume [3.5 ± 2.7 (15-35) ml vs. 13.1 ± 6.1 (4-25) ml] and mean surgical time [7.6 ± 4.5 (2-23) min vs. 23.6 ± 4.4 (15-35) min] in the Device Group were significantly less than in the Control Group (P<0.01). No AEs were observed in either group. There were no significant differences in postoperative pain, healing, or satisfaction with penis appearance between groups (P>0.05). CONCLUSIONS: This novel disposable circumcision device produced satisfactory preliminary adult MC results compared with CDT treatments. This device may be broadly used in men, such as those with phimosis, who are ineligible for CDT.