Castration-resistant prostate cancer (CRPC) is a considerable clinical challenge, driven by complex molecular mechanisms that enable tumors to evade androgen deprivation therapy. This review explores the molecular mechanisms driving CRPC progression, focusing on androgen receptor (AR) signaling, cancer stem cells (CSCs), and neuroendocrine differentiation (NED). In AR-dependent CRPC, AR signaling remains pivotal in disease progression. Mutations, splice variants, alternative pathways, and transcriptional regulation facilitate sustained AR activation despite androgen deprivation therapy. In addition, CSCs promote tumor recurrence and treatment resistance by maintaining cellular heterogeneity and evading conventional therapies. Furthermore, castration-resistant neuroendocrine prostate cancer, an aggressive subtype of CRPC, is characterized by AR independence and NED, making treatment challenging. These findings underscore the need for therapeutic strategies targeting AR-, CSC-, and NED-specific mechanisms. Crucially, the molecular classification of CRPC into AR-dependent CRPC, stem cell-like CRPC, and castration-resistant neuroendocrine prostate cancer subtypes—based on the interplay between AR signaling, CSCs, and neuroendocrine features—is essential for advancing precision medicine. Tailoring treatments to the molecular subtype and characteristics of each patient offers the potential to substantially improve prognosis and survival in CRPC.
Background: Metabolic alterations and inflammatory processes contribute substantially to the pathogenesis of prostate cancer (PCa). This study used Mendelian randomization (MR) to investigate the causal relationships between plasma metabolites and PCa and to identify potential mediators, including immune cell traits and circulating inflammatory proteins.
Materials and methods: A 2-sample MR analysis was conducted using data from the Canadian Longitudinal Study on Aging and a diverse genome-wide association study of PCa. A total of 1400 plasma metabolites were analyzed. Single-nucleotide polymorphisms were carefully selected and refined using linkage disequilibrium clumping. The inverse variance weighting method was used for primary analysis, supplemented by sensitivity analyses, including MR-Egger, weighted median, and MR-Pleiotropy RESidual Sum and Outlier, to ensure the robustness of the results.
Results: Eight metabolites were significantly associated with PCa. Specifically, a higher phosphate-to-uridine ratio was associated with a decreased risk of PCa, whereas higher levels of N- acetyl-arginine were linked to an increased risk. Other significant metabolites included the phosphate-to-2′-deoxyuridine ratio; N6-methyl-lysine, N-acetyl-leucine, N- succinyl-phenylalanine, and cysteinylglycine disulfide levels; and the α-ketoglutarate-to-ornithine ratio. Sensitivity analyses and the MR-Steiger test confirmed the robustness and causal direction of these associations. In addition, further analysis indicated that certain metabolites may influence PCa risk by modulating the expression of inflammatory markers, such as leukemia inhibitory factor receptor, interleukin-8, and CD33-related markers.
Conclusions: This study identified plasma metabolites that exert causal effects on the risk of PCa and highlighted the mediating role of immune traits and inflammatory proteins. These findings underscore the complexity of the biological pathways involved and suggest potential targets for therapeutic interventions.
Background: Survival in patients with prostate cancer (PCa) is now significantly prolonged. However, the incidence of secondary primary malignancies (SPMs) has increased during the treatment for PCa, which adversely affects patient survival. This study explored the factors influencing the overall survival (OS) of SPM in patients with nonmetastatic PCa and the impact of SPM with different histologic types on OS.
Materials and methods: We evaluated the clinical data of patients diagnosed with PCa of T1N0M0 to T4N0M0 between 2010 and 2015 from the Surveillance, Epidemiology, and End Results database. The patients were divided into 2 groups: with or without SPM. The key risk factors affecting OS were analyzed using Cox regression analysis. To mitigate the influence of other confounding factors, we performed propensity score matching in a 1:1 ratio. The Kaplan-Meier method was used to assess the impact of SPM on OS across different histological types.
Results: In total, 208,984 patients with nonmetastatic PCa were enrolled, including 16,573 and 192, 411 patients in the SPM and non-SPM groups, respectively. Age (p < 0.05), chemotherapy (p = 0.010), presence of SPM (p < 0.05), Gleason score of the biopsy specimens (p < 0.05), and prostate-specific antigen levels (p < 0.05) were identified as independent risk factors for OS. Conversely, race (p < 0.05), radical prostatectomy (p < 0.05), and radiotherapy (p < 0.05) were independent protective factors of OS. The 5-year OS rate was worse in the SPM group than in the non-SPM group (72.9% vs. 91.2%, p < 0.05). Patients with SPM of the pulmonary and bronchial types have the worst long-term prognosis, whereas those with SPM of cutaneous melanoma have the best prognosis.
Conclusions: During the management of patients with PCa, we must extend our attention beyond potential PCa recurrence and metastasis to the possibility of SPM, which compromises patient survival.
Robot-assisted kidney transplantation (RAKT) is a new, minimally invasive option for kidney transplantation with great application prospects. This narrative review aimed to outline the developmental history of RAKT, existing technology, and its application in different types of kidney transplant surgery. The challenges with RAKT and the solutions to those challenges in practical operation are analyzed as well, to provide reference for the application of robots in kidney transplantation.
Background: Urinary tract infections (UTIs) are common infectious disorders affecting 50% of healthy women at least once during their lifetime. Antibiotic treatment for UTIs may increase the prevalence of antimicrobial resistance and side effects, highlighting the need for safe and efficacious alternatives. This study investigated the effect of acute supplementation with UClear, a D-mannose product, on UTI symptoms.
Materials and methods: Women with at least 2 uncomplicated UTI symptoms, as assessed using the UTI Symptom Assessment (UTISA) questionnaire and urine nitrite and leukocyte testing, were randomized to receive UClear or a placebo for 3 days. The study outcomes included changes in the UTI symptom severity and bother scores, complete resolution of UTI symptoms, urine culture data, quality of life assessed using the RAND 36-Item Short Form Survey questionnaire, and rescue medication use. Study outcomes were measured from baseline to days 2, 3, and 4.
Results: The total UTISA severity scores were not significantly different between the groups. Participants supplemented with UClear had lower total UTISA bother scores after 3 days than the placebo group (p = 0.027). On day 4, 43% of participants receiving UClear had complete resolution of “frequency of urination,” based on the severity scores, compared with 20% of participants receiving the placebo (p = 0.032). A greater proportion of participants supplemented with UClear reported improvements in the severity and bother scores of “incomplete voiding” (p ≥ 0.020) and “urgency of urination” (p ≥ 0.059), compared with the placebo group. The proportion of participants in the UClear group with urinary microbial growth improved from 50% at baseline to 29% by day 4 (p = 0.020). UClear supplementation was safe and well tolerated.
Conclusions: After 3 days of UClear supplementation, urination-related UTI symptoms improved compared with those of the placebo group. These improvements corresponded with significant improvements in the degree of discomfort due to those symptoms. Further investigations in at-risk populations are warranted to understand the efficacy of UClear in resolving UTIs.
Background: Robot-assisted kidney transplantation (RAKT) has currently become an effective alternative to open kidney transplantation (OKT), which has long been considered the gold standard for kidney transplant surgery. This study aimed to summarize our initial experience with RAKT and explore its safety and feasibility.
Materials and methods: Ten cases of RAKT, including 8 cases of deceased-donor kidney transplantation and 2 cases of living-donor kidney transplantation, were performed at our center from March 2023 to November 2023. Perioperative clinical data and follow-up results of patients were collected and statistically analyzed.
Results: All RAKT surgeries were performed successfully with no complications. The average operative time was 297.90 ± 65.59 minutes, and the median estimated blood loss was 100 mL. The average serum creatinine level decreased from 918.14 ± 166.63 μmol/L preoperatively to 109.89 ± 29.89 μmol/L at discharge. The postoperative outcomes of RAKT from both deceased and living donors were satisfactory during the follow-up period.
Conclusions: Robot-assisted kidney transplantation is an effective alternative to OKT and is suitable for both deceased- and living-donor kidney transplantations. The short-term postoperative follow-up results were satisfactory, and the postoperative complications were acceptable. Robot-assisted kidney transplantation appears to be a safe and feasible procedure for transplantation teams skilled in OKT and robot-assisted surgery. This study is an exploratory research providing preliminary experience, and future large-sample controlled studies are needed to further verify its safety.