Fourth International Consultation On Incontinence (ICI) - Pathophysiology Committee Highlights

Main Category: Urology / Nephrology
Article Date: 25 Jul 2008 - 2:00 PDT

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PARIS, FRANCE (UroToday.com) - Dr. Koelbl began the last presentation of the morning session by discussing the various etiologies for detrusor overactivity (neurogenic vs. non-neurogenic) and how different mechanisms are responsible.

Neurogenic DO is generally understood to be caused by decreased inhibitory input from the spinal cord or higher centers. Non-neurogenic DO has multiple etiologies including outlet obstruction, aging, pelvic floor disorders and others, all of which may involve different mechanisms.

With respect to outlet obstruction, there is a significant amount of animal data regarding the changes induced by obstruction, which include; partial denervation which leads to hypersensitivity to neurotransmitters, reorganization of the C-fiber mediated spinal micturition reflex and changes in the detrusor muscle and urothelium which are pro-contractile. In the aging bladder studies have shown altered detrusor muscle cell protrusion junctions, a decreased B3 mediated relaxation response, and altered neurotransmition including increased ATP release and decreased Ach release. Estrogen deficiency has been shown to lead to decreased compliance and increased urothelial ATP release during filling, both of which may contribute to DO. The proposed mechanism by which pelvic floor disorders (SUI) may contribute to DO by the urethral-spinal-bladder reflex. The various mechanisms which may be involved with idiopathic DO were noted with emphasis placed on the recent abundance of work regarding increased afferent signaling. Consistent with the other presentations this morning, this may involve urothelial or myogenic mechanisms.

The discussion then moved on to pelvic organ prolapse and a review of the proposed risk factors, most significantly childbirth, parity, obesity and hysterectomy. Hysterectomy was associated with a 5.5 times increased risk of POP. Colposuspension and sacrospinous ligament fixation also increased risk of subsequent POP. Estrogen therapy may promote UI but not POP. There may also be genetic factors, as an increased incidence is noted in relatives with POP. This may be related to differential gene expression of myosin, actin and elastin. It was also noted that POP is common in patients with connective tissue disorders such as Ehlers-Danlos syndrome.

Dr. Koelbl then reviewed our current understanding of the urinary continence mechanism and the currently favored "integral theory" of Petros and Ulmsten. Notable risk factors include gender, age, childbirth/parity, obesity, coughing, heavy lifting, hysterectomy and genetic factors. There are age-related changes to pelvic floor musculature including a loss of rhabdosphincter muscle mass. There are changes in periurethral collagen composition in women with SUI including a lower ration of type I:type III collagen and changes in elastic fiber metabolism and gene expression. Newer studies show increased levels of tenascin and matrix mettaloproteinases, which may be caused by POP, in women with SUI. Next he reviewed the levels of anatomic pelvic support and the various defects involved in POP. He discussed anterior prolapse and UI, and cystocele correction will cure SUI in 2/3 of patients. POP reduction yields occult SUI rates of 23-63% during testing, and pessary reduction appears to be the best predictor of post-operative post-void residuals. Much attention was paid to pregnancy and childbirth and the effects on the pelvic floor. Dr. Koelbl stated that 50% of women develop UI during pregnancy and that antenatal UI predisposes to postpartum UI. Grand parity predisposes to SUI. Early postpartum prevalence rates are 9-31%. Cesarean section appears to be protective, but this effect diminishes with further deliveries. Several studies were highlighted including one which showed a 35% incidence of stage II POP after secondary cesarean section compared with 32% after vaginal delivery. A different study showed reduced POP and POP symptoms after cesarean section compared with vaginal delivery. Specific perinatal risk factors include parity, birth weight and type of delivery. Episiotomy, contrary to popular opinion, does not appear to be protective. Episiotomy is associated with increased postoperative pain and bleeding, and a higher incidence of 3rd and 4th degree perineal tears with midline episiotomy. Most of the damage to the pelvic floor appears to be associated with the first pregnancy/delivery, and increased PTNML and decreased PFM strength after delivery but most return within sev. Mos. Epidural analgesia is associated with a higher rate of perineal injury due to prolonged 2nd stage of labor and increased use of instrument delivery. However, there does not appear to be an increased incidence of SUI postpartum.

He next outlined the committee's findings regarding the pathophysiology of SUI. SUI was found in a recent study to be associated with increased genitohiatal measurement on ultrasound. 2 relatively new urodynamic studies were described including the association of the relationship of opening vesical pressure to ISD and lower urethral resistance pressures in women with SUI. Women with SUI were also show to have reduced pelvic floor muscle activity and lower urethral closure pressures after repeated coughs. Other studies showed differential elastin gene expression in women with SUI, and decreased alpha-2 mRNA and protease inhibitory activity in the vaginal wall in women with SUI. Ultrasonographic sphincter volume correlated with the degree of incontinece during videourodynamics, however results on urethral vasculature in SUI were conflicting.

The next portion of the presentation focused on incontinence in men and the obvious differences compared with women. Detrusor overactivity and OAB in men is often secondary to prostatic obstruction, and DO may resolve in 70% of patients after BOO is treated. Changes in neurotransmission and mechanical properties of the bladder may contribute to persistent DO in some.

With respect to SUI in men, this is noted to be almost exclusively in men with a history of prostate surgery or neurological disease. The proposed etiologies of post-prostatectomy incontinence include direct injury, thermal injury, nerve injury or damage from ablative technologies such as cryotherapy, HIFU or radiation. Level 2 evidence from the U.S. Agency for Health Care Policy and Research 1994 Clinical Guidelines gave a prevalence of 2.1% for post-TURP SUI. Level 1 evidence exists showing no differences in rates of incontinence after TURP vs. KTP laser prostatectomy and TURP vs. holmium laser resection. Incontinence is much more common after TURP following treatments for prostate cancer including brachytherapy and external beam radiotherapy. Rates of incontinence after radical prostatectomy are much more variable and depend on definitions, surgeon expertise and method of data collection. Medicare data from 1988-1990 showed that 31% of patients wore pads or clamps. Numbers from centers of excellence are generally much better, generally less than 10%. There is Level 1 evidence which did not show a difference in incontinence outcomes in laparoscopic versus open radical prostatectomy. Data is accumulating with respect to robotic radical prostatectomy and is generally similar to open surgery, although this was not addressed in this presentation.

Finally, Dr. Koelbl reviewed the pathophysiology of fecal incontinence. Special attention was paid to the role of childbirth and the concept of occult anal sphincter injuries (OASIS). Fecal incontinence is present in 5-26% of women in the first year after vaginal delivery. This is thought to be due to mechanical and neurological birth injuries. With respect to OASIS, there is some controversy regarding its role in FI and the predictive value of testing. 10 studies were listed examining primiparous women before and after birth with a mean rate of 27% for OASIS. However, another study by Andrews et al (2006) showed that almost all perineal injuries could be detected by careful examination after delivery and 8 weeks postpartum (N=241). A review of 35 studies on primary repair of OASIS showed a mean rate of FI of 14%. Several Level 1 recommendations were made by the committee regarding perinatal management and FI. Vacuum extraction appears to be superior to forceps in preventing anal sphincter and perineal trauma, lateral episiotomy is superior to midline episiotomy in preventing anal sphincter rupture, and liberal use of episiotomy is not beneficial. The "overlap" technique of anal sphincter repair seems to be superior to end-to-end repair.

Heinz Koelbl, MD, Committee Chair

Moderated by William C. de Groat, Ph.D., Professor, and L. Denis, MD, at the Fourth International Consultation on Incontinence (ICI) - July 5 - 8, 2008. Palais des Congres, Paris, France.

Written by William Jaffe, MD, a Contributing Editor with UroToday.

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