Stress urinary incontinence is still a frequent problem for women and men, which leads to pronounced impairment of the quality of life and withdrawal from the social environment. Modern diagnostics and therapy improved the situation for individuals affected. But there are still limits, including the correct diagnosis of incontinence and its pathophysiology, as well as the therapeutic algorithms. In most cases, patients are treated with a first-line regimen of drugs, possibly in combination with specific exercises and electrophysiological stimulation. When conservative options are exhausted, minimally invasive surgical therapies are indicated. However, standard surgeries, especially the application of implants, do not pursue any causal therapy. Non-absorbable meshes and ligaments have fallen into disrepute due to complications. In numerous countries, classic techniques such as colposuspension have been revived to avoid implants. Except for tapes in the treatment of stress urinary incontinence in women, the literature on randomized controlled studies is insufficient. This review provides an update on pharmacological and surgical treatment options for stress urinary incontinence; it highlights limitations and formulates wishes for the future from a clinical perspective.
What's known on the subject? and What does the study add?: Sacral neuromodulation ( SNM ) is an effective treatment option of different pelvic‐related dysfunctions. SNM evaluation by either temporary or permanent electrodes is generally accepted. Extended testing with temporary electrodes has been reported on before but less is known about infection‐related risks during prolonged evaluation with definitive electrodes. The present findings show that prolonged testing (mean = 52.3 days) with permanent electrodes does not increase infection‐associated explantation rates, although bacterial colonization was found in more than one‐third of the patients. Prolonged SNM evaluation under everyday conditions might improve long‐term success. Objective: To evaluate the impact of prolonged stage 1 testing on bacterial electrode colonization, infection and treatment success. Materials and Methods: In all, 21 patients who underwent sacral neuromodulation ( SNM ) for periods ≥1 month were prospectively evaluated; nine patients had overactive bladder syndrome ( OAB ), 10 had urinary retention, two had faecal incontinence ( FI ), and 13 had diabetes and overweight/obesity. After stage 1 testing electrode extension leads were microbiologically analysed to assess bacterial colonization. The primary measurements were pre‐ and post‐ SNM treatment comparisons based on patient‐agreed criteria using an increased 70% minimum improvement rate; secondary measurements were bacterial colonization and impact of infection. Results: The mean stage 1 evaluation period was 52.3 days; 16 patients (76%) progressed to stage 2, and five patients were explanted due to inadequate improvement (<70%). There was bacterial colonization in 42.9% of patients and 38.2% of extension leads. Stage 2 patients showed no infection or wound‐healing disorders at a mean follow‐up of 33.9 months. The success rate for stage 2 implantation treatment was 94%. Conclusions: There are few studies in the literature evaluating SNM testing periods vs the risk of clinically relevant implant infection rates. The present study shows that prolonged testing could potentially enhance treatment efficacy without infection‐related explantations of the chronic implant, despite the identification of bacteria. SNM ‐implanted patients with diabetes mellitus or obesity should be followed closely. Clinicians might consider using prolonged testing under everyday conditions. Prolonged SNM stage 1 testing is a very effective minimally invasive treatment option to evaluate pelvic‐related dysfunction.
This study investigates the feasibility of establishing urine-derived tumor organoids from bladder cancer (BC) patients as an alternative to tissue-derived organoids. BC is one of the most common cancers worldwide and current diagnostic methods involve invasive procedures. Here, we investigated the potential of using urine samples, which contain exfoliated tumor cells, to generate urine-derived BC organoids (uBCOs). Urine samples from 29 BC patients were collected and cells were isolated and cultured in a three-dimensional matrix. The establishment and primary expansion of uBCOs were successful in 83% of the specimens investigated. The culturing efficiency of uBCOs was comparable to cancer tissue-derived organoids. Immunohistochemistry and immunofluorescence to characterize the uBCOs exhibited similar expressions of BC markers compared to the parental tumor. These findings suggest that urine-derived BC organoids hold promise as a non-invasive tool for studying BC and evaluating therapeutic responses. This approach could potentially minimize the need for invasive procedures and provide a platform for personalized drug screening. Further research in this area may lead to improved diagnostic and treatment strategies for BC patients.
Stress urinary incontinence is a significant social, medical, and economic problem. It is caused, at least in part, by degeneration of the sphincter muscle controlling the tightness of the urinary bladder. This muscular degeneration is characterized by a loss of muscle cells and a surplus of a fibrous connective tissue. In Western countries approximately 15% of all females and 10% of males are affected. The incidence is significantly higher among senior citizens, and more than 25% of the elderly suffer from incontinence. When other therapies, such as physical exercise, pharmacological intervention, or electrophysiological stimulation of the sphincter fail to improve the patient’s conditions, a cell-based therapy may improve the function of the sphincter muscle. Here, we briefly summarize current knowledge on stem cells suitable for therapy of urinary incontinence: mesenchymal stromal cells, urine-derived stem cells, and muscle-derived satellite cells. In addition, we report on ways to improve techniques for surgical navigation, injection of cells in the sphincter muscle, sensors for evaluation of post-treatment therapeutic outcome, and perspectives derived from recent pre-clinical studies.
Generation of organoids from urinary tract tumor samples was pioneered a few years ago. We generated organoids from two upper tract urothelial carcinomas and from one bladder cancer sample, and confirmed the expression of cytokeratins as urothelial antigens, vimentin as a mesenchymal marker, and fibroblast growth factor receptor 3 by immunohistochemistry. We investigated the dose response curves of two novel components, venetoclax versus S63845, in comparison to the clinical standard cisplatin in organoids in comparison to the corresponding two-dimensional cultures. Normal urothelial cells and tumor lines RT4 and HT1197 served as controls. We report that upper tract urothelial carcinoma cells and bladder cancer cells in two-dimensional cultures yielded clearly different sensitivities towards venetoclax, S63845, and cisplatin. Two-dimensional cultures were more sensitive at low drug concentrations, while organoids yielded higher drug efficacies at higher doses. In some two-dimensional cell viability experiments, colorimetric assays yielded different IC50 toxicity levels when compared to chemiluminescence assays. Organoids exhibited distinct sensitivities towards cisplatin and to a somewhat lesser extent towards venetoclax or S63845, respectively, and significantly different sensitivities towards the three drugs investigated when compared to the corresponding two-dimensional cultures. We conclude that organoids maintained inter-individual sensitivities towards venetoclax, S63845, and cisplatin. The preclinical models and test systems employed may bias the results of cytotoxicity studies.