A Protocol for Organoids from the Urine of Bladder Cancer Patients.

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.

Minimally invasive prostatic urethral lift (PUL) efficacious in TURP candidates: a multicenter German evaluation after 2 years.

INTRODUCTION: Successful outcomes have been reported for the treatment of lower urinary tract symptoms (LUTS) with the prostatic urethral lift (PUL) in a number of clinical investigations. Our aim was to investigate PUL outcomes in patients treated in a day-to-day clinical setting without the rigid exclusion criteria of clinical studies. MATERIALS AND METHODS: We investigated the outcome of the PUL procedure at five German departments during the initial period when PUL was approved for the clinic (10/2012-06/2014). All candidates for transurethral resection of the prostate (TURP) received PUL information and were given the choice of procedures. The only exclusion criterion was an obstructive median lobe. No patients were excluded because of high post-void residual volume (PVR), prostate size, retention history or LUTS oral therapy. Maximum urinary flow (Qmax), PVR, International Prostate Symptom Score (IPSS) and Quality of Life (QOL) were assessed at baseline, 1, 6, 12, and 24 months after surgery. RESULTS: Of 212 TURP candidates, 86 choose PUL. A mean of 3.8 (2-7) UroLift implants were implanted in patients of 38-85 years with a prostate size of 17-111 ml over 57 (42-90) min under general or local anesthesia. Thirty-eight (38.4%) patients had severe BPH obstruction and would have been denied PUL utilizing previously reported study criteria. Within 1 month 74 (86%) reported substantial symptom relief with significant improvements in Qmax, PVR, IPSS, and QOL (p < 0.001) that was maintained within the follow-up. Sexual function including ejaculation was unchanged or improved. No Clavien-Dindo Grad ≥ 2 was reported postoperatively. Eleven (12.8%) patients were retreated over 2 years. Twelve (86%) of 14 patients presenting with chronic urinary retention were catheter free at last follow-up. CONCLUSION: PUL is a promising surgical technique that may alleviate LUTS, even in patients with severe obstruction.

Prolonged percutaneous SNM testing does not cause infection-related explanation.

UNLABELLED: 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.

How does neuromodulation work.

Although sacral neuromodulation (SNM) is approved and successfully used for different urological and proctologic functional diseases for the long-term treatment, less is known about the working mechanisms underlying SNM. This review highlights SNM clinical application, the current data of LUT neuroanatomy and neurophysiology, SNM techniques and its prospective working mechanisms. Functional imaging techniques have facilitated a more detailed insight into the neural network between the central nervous system (CNS) and the lower urinary tract (LUT). In addition to the well-known factors of the spinal micturition pathway, several pontine (e.g. pontine micturition centre) and suprapontine (e.g. cingulate cortex) regions and their interactions have been identified. An attribution of CNS activity levels to different LUT conditions is possible for the first time. Based on this information, different SNM actions could also have been allocated to different ascending/descending pathways and supraspinal regions, whereas acute SNM especially affects regions of learning activity, chronic SNM might result in CNS plasticity even though clinical effectiveness fades after SNM deactivation. Studies to treat fecal incontinence or to prevent detrusor overactivity in complete spinal cord injured patients support the importance of sympathetic pathways for the action of SNM. Despite increasing knowledge about SNM influence on the CNS, the complexity of its underlying working mechanisms is not understood at all. Further investigations with improved functional imaging techniques will enhance our SNM background.

Early sacral neuromodulation prevents urinary incontinence after complete spinal cord injury.

BACKGROUND: The study aim was to investigate potential influences on human nerves and pelvic organs through early implantation of bilateral sacral nerve modulators (SNMs) in complete spinal cord injury (SCI) patients during the acute bladder-areflexia phase. METHODS: Ten patients with neurologically-confirmed complete spinal cord lesions (SCLs) were provided with bilateral SNMs during the phase of atonic-detrusor muscle. Modulation was achieved by two electrodes implanted into each S(3)-foramen. Six patients declined and served as controls. The mean follow-up was 26.2 months. RESULTS: Videourodynamics (VU) confirmed detrusor acontractility, resulting in urinary continence as well as significant reductions in urinary tract infections (UTIs). Bowel movements did not require oral laxatives; additional preprogrammed parameters achieved erections for intercourse. INTERPRETATION: Early SNM implantation in SCI patients may revolutionize neurogenic lower urinary tract (LUT) dysfunction management; it prevented detrusor overactivity and urinary incontinence, ensured normal bladder capacity, reduced UTI rates, and improved bowel and erectile functionality without nerve damage. CONCLUSION: Future SCI investigations will be conducted to evaluate the potential benefits of even earlier SNM placement to progressively enhance pelvic organ functionality. This new approach may provide important clues required for assessing whether neuronal information is passed through the sympathetic trunk ganglion to the brain after complete SCI. Further investigations are needed to determine if functional magnetic resonance imaging (fMRI) might be helpful for analyzing changes in brain function in patients with SNMs and those taking antimuscarinics.