John Heesakkers

A New, Straightforward Ex Vivo Organoid Bladder Mucosal Model for Preclinical Research

PURPOSEnWe developed an experimental ex vivo organoid bladder mucosal model that can be used for experimental research purposes to create alternatives to current animal models.nnnMATERIALS AND METHODSnWe developed an ex vivo organoid bladder mucosal model by immobilizing a type I collagen scaffold on the bottom of a Transwell® insert, creating a 2-compartment system. Mucosal biopsies from porcine bladders were placed on top of the scaffold and cultured in different mediums. We evaluated the morphological aspects of biopsy tissue. Cultured samples were assessed by scanning electron microscopy, and immunohistochemical and histochemical staining for cell identification, proliferation and morphology.nnnRESULTSnCells remained viable in Dulbeccos modified Eagles medium/F-12 and smooth muscle cell medium for up to 3 weeks. The mucosa retained normal morphological characteristics for up to 1 week. Cells (mostly urothelial cells) proliferated and fully covered the scaffold surface within 3 weeks.nnnCONCLUSIONSnWe developed an experimental ex vivo organoid model of bladder mucosa for preclinical experimental research. This model could be used for high volume screening for pharmacology and toxicology experiments. It has the potential to replace currently used animal models.

Three-months results of implant driven tibial nerve stimulation for the treatment of overactive bladder syndrome

Study design, materials and methods Included patients are part of a multicentre trial. This abstract will describe the 3 months results of the patients treated in our hospital. In 15 OAB patients a battery free stimulation device for tibial nerve stimulation (BlueWind Medical,Herzliya, Israel) was implanted. The system composed of an implant, which is wirelessly powered by an external control unit (ECU) that controls the therapeutic parameters and is worn by the patient during treatment at home. A Physician Programmer is used to remotely set individual stimulation parameters for each patient to optimize therapeutic outcome. One month after implantation the system was activated using standard parameters, a pulse width of 200μsec and a frequency of 20Hz. The patient specific minimum amplitude was set at the amplitude of first sensation, and the maximum amplitude was set at the highest tolerable level. Patients were asked to stimulate 6 times a week for 30 minutes at a comfortable amplitude. Patients received an ECU in order to operate the implant and be able to adjust the amplitude between a patient specific set minimum and maximum. Follow up visits were planned 1 and 3 months after activation with a 3-day bladder diary and quality of life questionnaire. In addition to the multicentre protocol patients filled in a 3-day 24-hour pad test, ICIQ-FLUTS questionnaire and the patient perception of bladder condition (PPBC). The bladder diary contained frequency, micturition volume, fluid intake, and the number and severity of urinary urgency episodes (range 1-5, 5=high) as well as incontinence episodes (0= no leak, 1= drops, 2= small amount, 3=large amount). The ICIQ-FLUTS consists of 12 questions on bladder filling, voiding and incontinence. Each question allows five response options: ‘never’ (0), ‘occasionally’(1), ‘sometimes’ (2), ‘most of the time’ (3), and ‘always’ (4). The total sum score of the ICIQ-FLUTS ranges from 0-48 (asymptomatic to very symptomatic). Each question on symptoms is linked to a question on bother from 0-10 (no bother – maximum bother). The total sum score of the ICIQ-FLUTS on bother ranges from 0-120. The PPBC is a single-Item global measure for patients with OAB. Patients are asked to rate their perceived bladder condition on a 6-point scale. ‘no problem at all’ (1), ‘very minor problems’ (2), ‘minor problems’ (3), ‘moderate problems’ (4), ‘severe problems’ (5), ‘many severe problems’ (6). If necessary 1 month after activation the stimulation parameters were adjusted.

Pilot study of subject controlled percutaneous dorsal genital nerve stimulation for the treatment of idiopathic urgency incontinence

Hypothesis / aims of study NICE have recently highlighted the importance of better predicting outcome from disobstructive surgery in clinical guideline 97. Given that men with urodynamically proven bladder outlet obstruction (BOO) experience better outcome, this could be achieved by increasing the diagnostic accuracy of clinical tests used during the workup to surgery. An individual’s average maximum flow rate (Qmax) from multiple measurements will have better diagnostic accuracy for BOO than a single value because the influence of outliers and unrepresentative measurements is reduced [1]. However, in general the value of Qmax is weakened by its dependence on bladder volume. Attempts to address this have been made by correcting Qmax for voided volume (Vvoid), or categorising the [Qmax,Vvoid] pair using relationships derived from large groups of men [2]. However, given that the relationship differs for each man, this may not improve accuracy. The aim of this study was to determine whether a personalised volume-corrected Qmax can better predict outcome from disobstructive surgery than an individual’s mean Qmax, both measurements being derived from home uroflowmetry.