RESUMEN
The decline of urethral function with advancing age plays a major role in urinary incontinence in women, impairing quality of life and economically burdening the health care system. However, none of the current urinary incontinence treatments address the declining urethral function with aging, and the mechanisms by which aging impacts urethra physiology remain little known or explored. Here, we have compared functional, morphometric, and global gene expression of urethral tissues between young and old female mice. Bladder leak point pressure (LPP) measurement showed that the aged female mice had 26.55% lower LPP compared to younger mice. Vectorized Scale-Invariant Pattern Recognition (VIPR) analysis of the relative abundance of different tissue components revealed that the mid-urethra of old female mice contains less striated muscle, more extracellular matrix/fibrosis, and diminished elastin fibers ratio compared to young mice. Gene expression profiling analysis (bulk RNA-seq of the whole urethra) showed more down-regulated genes in aged than young mice. Immune response and muscle-related (striated and smooth) pathways were predominantly enriched. In contrast, keratinization, skin development, and cell differentiation pathways were significantly downregulated in aged urethral tissues compared to those from young female mice. These results suggest that molecular pathways (i.e., ACVR1/FST signaling and CTGF/TGF-ß signaling) leading to a decreased striated muscle mass and an increase in fibrous extracellular matrix in the process of aging deserve further investigation for their roles in the declined urethral function.
RESUMEN
Objectives: To present a case of foreign body granuloma (FBG) development after injection of calcium hydroxylapatite as a urethral bulking agent and to review all documented cases of this phenomenon in the literature. Methods: We analyzed a new case of calcium hydroxylapatite-induced FBG. We also conducted a literature review of the PubMed, Embase, CINAHL, and Web of Science databases through March 2022. Reports were included if they contained stress urinary incontinence patients that developed an FBG after calcium hydroxylapatite injection. The cases were reviewed for presenting symptoms, patient demographics, granuloma details, and surgical treatment. Results: We screened 250 articles and included six articles between 2006 and 2015 in addition to the present case. The median age of the patients was 65.5 years (range 45-93), and all patients were female. The most common presenting symptoms and the proportion of patients affected were difficulty voiding (4/8), recurrent urinary incontinence (3/8), and dyspareunia (2/8). The median time between the first CaHA injection and discovery of the FBG was 5 months (range 1-50). The median longest dimension of the FBGs was 1.85 cm (range 1.0-3.0). The 8 masses observed were evenly distributed throughout the urethra, with 3 in the bladder neck, 2 in the midurethra, and 3 in the distal urethra. Surgical excision was the predominant management choice, with some variation in technique. Conclusions: Severe, persistent lower urinary tract symptoms after calcium hydroxylapatite injection may indicate an FBG, which has been successfully managed with surgical excision.
