NSAUA 2018: Rehabilitation of the Atonic Bladder

Toronto, Ontario (UroToday.com) Michael Chancellor, MD gave an overview of the treatment of the atonic bladder (underactive bladder manifesting with difficulty in voiding).  The causes of underactive bladder include:

  • Neurological disease – Parkinson, diabetes, spinal cord injury and spina bifida.
  • Aging
  • Men with enlarged prostates, and those with prostate cancer with the ensuing therapy complications
  • Women – after childbirth, menopause, and following hysterectomy and pelvic prolapse
Detrusor underactivity and increased post-void residual (PVR) volume are associated with aging. Approximately 22% of men and 11% of women over the age of 60 have difficulties with bladder emptying.1 Another study demonstrated that detrusor underactivity is found in 2/3 of incontinent institutionalized elderly persons.2 Figure 2 demonstrates the prevalence of self –reported difficulty emptying the bladder stratified by gender and age.


UroToday NSAUA2018 Self reported difficulty emptying bladder stratified by gender and age
Figure 1- Self-reported difficulty emptying bladder stratified by gender and age

One of the possible treatments for underactive bladder is an indwelling catheter. Unfortunately, catheters are associated with a myriad of complications, including urinary tract infection, urethral injury, stricture, and false passage, bleeding, epididymitis, bladder stones, and bladder cancer with long periods of an indwelling catheter.

Bethanechol is a parasympathomimetic choline carbamate that selectively stimulates anticholinergic muscarinic receptors without any effect on nicotinic receptors, and was surmised to cause bladder contraction and eventual bladder emptying. It was hypothesized in the past that this could be a good treatment option for underactive bladder. However, a meta-analysis of 2700 patients demonstrated that there is little benefit in this drug in treating or preventing underactive bladder.3 Possible reasons for this lack of effect include the fact that underactive bladder may represent an unresponsiveness of the detrusor muscle towards neurostimulation. There might be a need for agents that directly act on the detrusor smooth muscle. Another possible reason is that current agents might be under-dosed to be effective on the detrusor.

There are several surgical methods that have been suggested to effectively treat underactive bladder. These act on one of two possible mechanisms – either decrease the outlet resistance or improve bladder emptying. Potential surgical strategies to decrease outlet resistance include incision of the bladder neck and prostate, external sphincter defeating procedures (over-dilation, sphincterotomy, urethral stent placement), sphincter and pelvic floor botulinum toxin injection, and intra-urethral prosthesis with a pump. Surgical strategies attempting to improve bladder emptying include reduction cystoplasty (reducing bladder capacity by 80%), bladder myoplasty (muscle transfer), engineered bladder (biodegradable scaffold and cells seeding), and cellular therapy (stem cells transplantation).

Bladder myoplasty is mainly performed in Germany, and involves using a flap of the latissimus dorsi muscle from the back. In this procedure the latissimus muscle is fixated in the pelvis around the bladder, leaving 25% of the bladder uncovered, leaving the trigone and lateral pedicles free. After wrapping the bladder with this skeletal muscle, neurovascular connections are made (Figure 2). The idea behind this is that patients actively contract the lower abdominal musculature when they want to urinate. In a multicenter study of 24 patients followed for 46 months after undergoing this procedure, 16/24 (67%) patients regained spontaneous micturition without needing to perform clean intermittent catheterization (CIC).4

UroToday NSAUA2018 Latissimus Dorsi Muscle bladder myoplasty
Figure 2- Latissimus Dorsi Muscle bladder myoplasty

A novel idea of utilizing an engineered bladder scaffold seeded with cells was next described by Dr. Chancellor. The engineered bladder is anastomosed to the native bladder with sutures, and the entire implant is covered with fibrin glue ad omentum (Figure 3). Unfortunately, the phase 2 trial5 involving this technology, in children with spina bifida requiring entrocystoplasty, did not report favorable results, with no improvement in bladder capacity or compliance, and with associated serious adverse events.

UroToday NSAUA2018 Engineered bladder
Figure 3 – Engineered bladder

Another previously mentioned surgical procedure was the insertion of the inflow intraurethral valve-pump that has been FDA approved since 2015. It is indicated for use only in women with incomplete bladder emptying due to impaired detrusor contractility of neurologic origin. Unfortunately, the device needs to be replaced every month. Data has shown that over half of the women had stopped using the device due to discomfort and leakage of urine. Furthermore, adverse effects included urinary tract infections, bladder inflammation, pain, hematuria, urinary leakage, frequency and urgency, and bladder spasms.

Dr. Chancellor then discussed the research and developments occurring in his own institution, with the establishment of a lab dedicated to underactive bladder research. The goals of the lab are to identify biomarkers for early diagnosis and validate preclinical models. One of the trials Dr. Chancellor developed is the Stem Cell clinical trial, which entails autologous transplantation of muscle-derived cells for an underactive bladder. Other research projects include various animal models for studying underactive bladder. Lastly, Dr. Chancellor aims to develop a specific underactive bladder questionnaire for clinical use.

Underactive bladder might share a common pathway with overactive bladder. Both share symptoms and are associated with common underlying etiologies such as aging, bladder outlet obstruction, and diabetes, and both can occur together in the form of detrusor hyperactivity with impaired contractility (DHIC). Dr. Chancellor believes that overactive bladder, underactive bladder, and DHIC all exist in the same common pathway, with overactive bladder eventually resulting in DHIC which leads to underactive bladder.

Dr. Chancellor summarized his talk stating that there is currently an accelerated interest in underactive bladder research; both myogenic and neurogenic. Animal models exhibit that underactive bladder often demonstrates that overactive bladder leads to DHIC, which eventually results in an underactive bladder. There are currently several novel therapies in development with underactive bladder representing a great unmet need and opportunity in urology care and research.


Presented by: Professor Michael Chancellor, MD Beaumont Health System and Oakland University School of Medicine

References:
1. Diokno AC et al. J Urol 1986; 136: 1022-5
2. Tayloer JA et al. J AM Geriat 2006; 54: 1920-32
3. Barendrecht et al. BJU Int. 2007
4. Gakis et al. J Urol 2011
5. Joseph et al. J Urol 2014

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan at the 70th Northeastern Section of the American Urological Association (NSAUA) - October 11-13, 2018 - Fairmont Royal York Toronto, ON Canada
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