Complications of treatment of obstetric fistula in the developing world: gynatresia, urinary incontinence, and urinary diversion.

OBJECTIVE: To provide a comprehensive review of the pathophysiology, evaluation, and treatment of gynatresia and urinary incontinence, 2 conditions that can arise following the repair of obstetric fistulas. The article discusses relevant issues with respect to urinary diversion in the treatment of obstetrical fistula and associated urinary incontinence. METHODS: A review was conducted of the existing literature and of the expert recommendations issued at the Gates Institute fistula meeting held in July 2005 at the Johns Hopkins Bloomberg School of Public Health. RESULTS: Gynatresia and urinary incontinence develop in approximately 10% and 16% of patients, respectively, after the first repair. Urinary diversion may be necessary when fistulas cannot be closed vaginally or in cases of severe urinary incontinence following successful closure. Gynatresia, urinary incontinence, and urinary diversion are all associated with morbidity, and they require surgical and nonsurgical expertise for proper management. CONCLUSIONS: Closing the anatomical fistula is not always sufficient, and treatment paradigms must shift toward the prevention and repair of gynatresia and urinary incontinence at the time of the primary operation.

Stress incontinence observed with real time sonography and dynamic fastscan magnetic resonance imaging--insights into pathophysiology.

Our concepts of pathophysiology of stress urinary continence have been greatly shaped by developments in radiographic imaging. Simple radiographs with and without contrast initially revealed the importance of urethral descent in pathogenesis. More recently, magnetic resonance imaging (MRI) and real time ultrasonography are showing soft tissue detail within both a global pelvic and a local urethral context. Careful examination of these studies can extend our concepts of pathophysiology and lead us beyond existing paradigms. We propose a unified theory of stress incontinence based on our dynamic fastscan MRI and real time ultrasonograms of stress incontinence, incorporating known details of pelvic anatomy, sphincteric location and function. The hypothesis introduces the concept of a continence threshold at which the urethra is subjected simultaneously to both shearing and explusive forces. If these forces are sufficient to overcome urethral coaptation at threshold, leakage results. The model proposes an anatomical sequence of changes through which the incontinent urethra cycles between periods of rest and increased abdominal pressure, and suggests a way in which repeated episodes of prolpase and urethral traction by shearing forces exerted by the vagina on the urethra may contribute to the development of intrinsic sphincteric deficiency.

Incidental non-Hodgkin's lymphoma in patients with localized prostate cancer.

OBJECTIVES: To determine the outcome of patients with clinically organ-confined prostate cancer undergoing radical retropubic prostatectomy for cure and incidentally discovered concurrent low-grade non-Hodgkin's lymphoma at time of surgery. METHODS: From September 1986 to September 1997, 4319 patients underwent radical retropubic prostatectomy at our institution. The records of 10 patients incidentally diagnosed to have low-grade non-Hodgkin's lymphoma at the time of radical prostatectomy were retrospectively reviewed. RESULTS: Of 4319 patients requiring radical prostatectomy, 10 (0.2%) were found to have low-grade non-Hodgkin's lymphoma. All 10 men had an uneventful postoperative course. Two patients subsequently developed progression of lymphoma, one of whom required treatment. One patient died of sepsis associated with his lymphoma and 1 patient died of an unrelated malignancy (lung cancer), both 7 years following surgery. Two patients developed biochemical prostate-specific antigen recurrence. The remainder of men were free of prostate cancer recurrence and experienced no progression of lymphoma at an average of 45 months (range 12 to 142). CONCLUSIONS: Patients with organ-confined prostate cancer, who are candidates for radical prostatectomy, experience long-term prostate cancer-free survival in the face of incidentally diagnosed low-grade lymphoma. Because the management of most incidentally discovered low-grade lymphomas is expectant, patients discovered at surgery to have this clinical entity should not be denied radical prostatectomy.

In situ anatomical study of the male urethral sphincteric complex: relevance to continence preservation following major pelvic surgery.

PURPOSE: We describe a correlative gross anatomical and histological study of the human male urethral sphincteric complex using methods that delineate skeletal, muscular and fascial components. MATERIALS AND METHODS: Pelves of 6 fresh frozen male cadavers were sectioned as 4 mm. tissue blocks in planes sagittal and perpendicular to the axis of the prostatomembranous urethra from the bladder neck to the bulb of the corpus spongiosum. Sections were photographed and prepared in situ for histological staining (hematoxylin and eosin, Masson's trichrome and phosphotungstic acid hematoxylin). RESULTS: The structure of the male urethral sphincteric complex was demonstrated to include the cylindrical rhabdosphincter surrounding the prostatomembranous urethra and a fascial framework, principally consisting of the ventral subpubic fascia and medial fascia of the levator ani musculature. The histological appearance of the rhabdosphincter at its dorsal aspect suggested a suburethral musculofascial plate. Rhabdosphincteric muscle fibers were oriented in vertical and ventrolateral directions with attachments to the subpubic fascia and the medial fascia of the levator ani. CONCLUSIONS: The structural components and their relationships suggest mechanisms whereby the complex is suspended and stabilized within the deep pelvis, and achieves urethral closure. Our study furthers an understanding of the anatomical basis for male urinary continence and micturition, and is expected to have primary importance in the effort to preserve urinary function following major pelvic surgery.

Female Stress Urinary Incontinence Clinical Guidelines Panel summary report on surgical management of female stress urinary incontinence. The American Urological Association.

PURPOSE: The American Urological Association convened the Female Stress Urinary Incontinence Clinical Guidelines Panel to analyze the literature regarding surgical procedures for treating stress urinary incontinence in the otherwise healthy female subject and to make practice recommendations based on the treatment outcomes data. MATERIALS AND METHODS: The panel searched the MEDLINE data base for all articles through 1993 on surgical treatment of female stress urinary incontinence. Outcomes data were extracted from articles accepted after panel review. The data were then meta-analyzed to produce outcome estimates for alternative surgical procedures. RESULTS: The data indicate that after 48 months retropubic suspensions and slings appear to be more efficacious than transvaginal suspensions, and also more efficacious than anterior repairs. The literature suggests higher complication rates when synthetic materials are used for slings. CONCLUSIONS: The panel found sufficient acceptable long-term outcomes data (longer than 48 months) to conclude that surgical treatment of female stress urinary incontinence is effective, offering a long-term cure in a significant percentage of women. The evidence supports surgery as initial therapy and as a secondary form of therapy after failure of other treatments for stress urinary incontinence. Retropubic suspensions and slings are the most efficacious procedures for long-term success (based on cure/dry rates). However, in the panel's opinion retropubic suspensions and sling procedures are associated with slightly higher complication rates, including longer convalescence and postoperative voiding dysfunction.

Anatomic goals in the correction of female stress urinary incontinence.

The goal of stress incontinence surgery is to prevent opening of the urethra during increases in intra-abdominal pressure. Greater refinements in the understanding of the pathophysiology of incontinence and experience with newer treatments have extended surgical thinking beyond the familiar paradigm "to place the urethra in a high retropubic position." When incontinence is associated with vaginal hypermobility, vaginal support may be sufficient to restore continence if the suburethral vaginal wall is sufficiently strong, an evaluation which must often be made by physical examination alone. However, when the vaginal wall is weak, the urethra will require an alternative form of support, usually a sling. If the urethra is intrinsically deficient, vaginal support may not be sufficient to prevent opening during increased intra-abdominal pressure, and coaptation by sling obstruction or periurethral bulking injection may be required. Most laparoscopic approaches to stress incontinence use Burch's method, which offers excellent urethral stability provided the suburethral vaginal wall is strong. Newer insights into the relation between vaginal mobility and urethral closure are discussed, as well as anatomic aspects of the Burch suspension relevant to laparoscopic repair.

Local recurrence and survival following nerve sparing radical cystoprostatectomy for bladder cancer: 10-year followup.

PURPOSE: The efficacy of nerve sparing radical cystoprostatectomy for the treatment of bladder cancer has been evaluated. We reviewed our 10-year experience with this technique to ascertain survival and local recurrence rates. MATERIALS AND METHODS: The charts of 101 patients treated with nerve sparing cystoprostatectomy between March 1982 and November 1989 were reviewed and updated. RESULTS: The disease-specific 10-year survival rate for all stages of bladder cancer treated was 69% and the 10-year survival rate free of local recurrence was 94%. Recovery of sexual function following nerve sparing cystectomy correlated with patient age: 62% in men 40 to 49 years old, 47% in men 50 to 59 years old, 43% in men 60 to 69 years old and 20% in men 70 to 79 years old. CONCLUSIONS: Nerve sparing radical cystoprostatectomy does not compromise cancer control and provides improved postoperative quality of life.

Radiography, sonography, and magnetic resonance imaging for stress incontinence. Contributions, uses, and limitations.

Imaging has increased our ability to understand stress incontinence and prolapse and has advanced our existing concepts of pathophysiology. Once these conceptual contributions have been made, imaging modalities may fade from current use, but the lessons learned will remain. It is the relationship of clinical imaging to conceptual development that is important. Conventional radiographic studies are well understood and can be obtained in most facilities. Sonographic units are currently available in many urologic and gynecologic clinics and offices and can be adapted for stress incontinence studies. The benefits of real-time studies and soft-tissue detail at the urethrovesical junction and office-based convenience make this an attractive new technique. The global pelvic approach offered by MR imaging offers spectacular imaging possibilities, which can help in complex cases and in future concepts in the field. MR imaging is rapidly evolving and may continue to offer new insights as technology permits. In accordance with Hodgkinson's earlier observations, imaging should not be routinely required in all patients undergoing evaluation for stress incontinence, but should certainly be considered in failed operations, complex prolapse, and when clinical diagnosis is in doubt. It is always better to use an imaging technique, no matter how expensive, than to end up with a bad surgical result.

Elastin morphology in normal and obstructed guinea-pig bladders. Localization of elastin to the trigone.

Elastin is the major component of elastic fibers in aortic tissue and has been suggested to be important for the stretch and recoil of the bladder. We have mapped the histologic distribution of elastin throughout the entire guinea-pig bladder as well as changes in the distribution of elastin during bladder-outlet obstruction. We used an animal model in which a jeweler's ring is placed around the urethra of the young guinea pig. As the animal grows, outlet obstruction is gradually induced, and the bladder gradually increases in total weight to as much as 8-fold that of controls. We localized the elastin histologically in normal and obstructed bladders by serially sectioning entire bladders and staining the sections with an elastin-specific stain, Verhoff-van Gieson stain (VVG). Surprisingly, we found that the elastin was predominantly localized only to the trigone of the bladder and that the elastin in this area was increased during obstruction. These results are consistent with the predominantly mesodermal embryologic origin of the trigone, since mesodermal tissues are more often associated with elastin expression.

Guinea pig as an animal model for the study of urinary bladder function in the normal and obstructed state.

The guinea pig has become an excellent model for the study of mechanical and electrical mechanisms regulating bladder function in the normal and obstructed state. Much preliminary work has been done on the in vitro behavior of the detrusor smooth muscle. The tissue has permitted electrophysiological studies by sucrose gap, microelectrode, and patch clamp technique. Excellent urodynamic studies can be performed under anesthesia. A recent model of bladder obstruction has resulted in a source of tissue which is suitable for electrophysiological analysis of the muscle. Low-cost and simple animal care requirements permit large-scale studies correlating urodynamic, structural, biochemical, contractile, and electrophysiological changes in response to obstruction.

A fetal lamb model of partial urethral obstruction: experimental protocol and results.

The functional effects of bladder outlet obstruction in the developing urinary tract are well recognized in patients born with posterior urethral valves, in whom a spectrum of bladder dysfunction has been described. To better understand the changes occurring in the partially obstructed developing lower urinary tract, a fetal lamb model of partial urethral obstruction was developed. Fetal lambs at 90 days' gestation underwent surgical placement of a silver ring (ex utero) at the level of the proximal bladder neck, with concomitant ligation of the urachus. Control animals underwent urethral ligation only. The lambs were then allowed to go through normal gestation, and ewes were delivered spontaneously. The animals were studied between 2 and 7 days after birth. The postmortem examination showed that the ring was just distal to the bladder neck, around the proximal urethra. This resulted in gradual, partial occlusion of the urethra. Bladder weights, bladder wall thickness, and bladder capacity were significantly increased in the partially obstructed animals as compared with the controls. There was little or no upper tract dilatation in the obstructed group. This animal model, the first to produce gradual outflow obstruction in the fetus, provides a reproducible model of partial urethral obstruction. The model can be used to assay the biochemical and physiological changes found in the developing urinary tract of fetal lambs submitted to intravesical obstruction.

Developmental alterations in the fetal lamb bladder subjected to partial urethral obstruction in utero.

To identify the structural changes seen in the developing bladder subjected to outflow obstruction, a fetal lamb model was developed. With this model, which attempts to reproduce conditions such as those found in posterior urethral valves, quantitative biochemical parameters were used to evaluate the effects of partial outflow obstruction on detrusor cellularity and innervation in the developing bladder. Partial urethral obstruction was created in 9 fetal sheep (90 to 100 days gestation), 6 sham operated animals serving as controls. Fetuses were delivered at term and sacrificed. Bladders were removed and weighed. Mucosa free detrusor was assayed for DNA and choline acetyltransferase (ChAT) activity, indices of cell number and cholinergic innervation, respectively. In similar specimens of detrusor, cell ploidy and nuclear size were determined by flow cytometry and nuclear morphometry, respectively. The results showed that partial urethral obstruction in utero resulted in a significant increase in bladder weight (p < 0.05) and total detrusor DNA content (p < 0.01). With the increase in detrusor DNA content, there was a parallel increase in total detrusor ChAT activity. These results suggest that early development of the bladder is altered both on a cellular level (increase in cellularity) and a neural level (increase in cholinergic nerve density) under conditions of mechanical distension.

Effect of partial urethral obstruction on force development of the guinea pig bladder.

We created gradual partial urethral obstruction in 20 guinea pigs using silver jeweler's jump rings. After 4 or 8 weeks obstruction all animals underwent cystometry and were assigned to one of five urodynamic categories: normal, high pressure voiding, unstable, low compliance, or decompensated. After sacrifice, the contractile responses of bladder strips to electrical field stimulation of intramural nerves, direct electrical muscle stimulation, 0.1 mM carbachol, and high K+ solution were sampled by computer for phase plot analysis. Following 8 weeks obstruction, the value of the phase plot parameter Fiso, indicative of the number of contractile muscle units, was reduced to 60% of the control response to nerve stimulation (P < 0.05) and to 77% of the control response to carbachol stimulation (P < 0.05). Parameter C, the slope of the phase plot (indicative of unit recruitment during force development), was unchanged for all forms of stimulation. Although in the latter case not statistically significant, obstruction affected responses to nerve and muscle stimulation similarly suggesting that muscle change may possibly be a common denominator of dysfunction. In view of the reduction in Fiso and the increase in bladder weight, instability may represent a more advanced form of dysfunction due to obstruction than high pressure voiding.

Detrusor hyperplasia and expression of "immediate early" genes with onset of abnormal urodynamic parameters.

To determine the stimulus for growth of the detrusor with a pathophysiological obstruction to the urinary stream, we studied urodynamic parameters, detrusor weight, detrusor DNA content, and the expression of early growth-related protooncogenes in a model of gradual onset bladder outflow obstruction and reversal of obstruction. Silver jeweler's jump rings were placed loosely round the urethra of immature guinea pigs, allowing an obstruction to develop gradually with animal growth. At 1, 2, 4, and 8 wk after surgery, animals were killed after urodynamic studies under urethan anesthesia. Bladders were removed, and mucosa-free detrusor was weighed and frozen for assay of DNA content and expression of c-fos and c-myc protooncogenes. Results were compared with sham-operated age-matched control animals. One week after surgery there was no change in the urodynamic parameters, detrusor weight, or DNA content. At 2, 4, and 8 wk after placement of the silver rings, animals developed obstructive voiding patterns, an increase in detrusor weight, and total DNA content. The onset of obstructive voiding patterns correlated with transient increased levels of c-fos and c-myc mRNA by Northern blot analysis. Autoradiography of in vivo [methyl-3H]thymidine-labeled detrusor muscle from obstructed animals showed myocyte DNA synthesis and mitosis, implying myocyte hyperplasia. After removal of the silver ring, the obstructive voiding patterns resolved and detrusor weight and DNA content returned to levels of the control animals. These results suggest that in the guinea pig bladder subjected to a gradual onset outflow obstruction, detrusor growth is initiated by the development of obstructive voiding patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of experimental urethral obstruction and its reversal on changes in passive electrical properties of detrusor muscle.

The passive electrical properties of guinea pig detrusor muscle were studied in order to determine how bladder outflow obstruction and reversal might modify the electrical activity of the bladder and, thus, contractility. Experimental bladder outflow obstruction was produced in guinea pigs and resulted in an increase in bladder weight with a decrease in spontaneous electrical activity, membrane time constant and space constant. In addition, the membrane Na-K pump activity increased with obstruction. Following reversal of obstruction, bladder weight gain associated with obstruction was only partially reversible. The decrease in the membrane time constant induced by obstruction was almost fully reversible following release of obstruction. In contrast, the membrane space constant which reflects spread of current, in addition to spontaneous electrical activity, were only partially reversible. The membrane Na-K pump activity of the detrusor muscle decreased to control levels following reversal of bladder outflow obstruction. There was no significant change in the resting membrane potential of detrusor smooth muscle with either obstruction or following reversal of obstruction. These results suggest, that, the changes in the bladder smooth muscle membrane electrical properties induced by experimental bladder outflow obstruction are only partially reversible following release of obstruction. Furthermore, the results suggest that, the dysfunctional cystometric patterns associated with bladder outflow obstruction might not only be due to changes in detrusor innervation but, fundamental reorganization of the detrusor's electrical syncytium with irreversible suppression of cell-to-cell transfer of electrical activity.

Effect of pinacidil on the membrane electrical activity of guinea pig detrusor muscle.

The effects of pinacidil on the guinea pig detrusor smooth muscle membrane were studied to investigate the electrophysiological mechanisms by which this drug relaxes smooth muscle tissue and, thus, might be of value in the treatment of detrusor instability. Pinacidil (> or = 3 x 10(-7) M) hyperpolarized the membrane in a concentration-dependent manner, with a reduction in spontaneous spike discharges. The membrane hyperpolarization induced by pinacidil was consistently associated with an increase in membrane ionic conductance. Glybenclamide (10(-6) M) completely inhibited the membrane hyperpolarization induced by pinacidil (up to 10(-5) M). Membrane hyperpolarization with pinacidil was consistently greater in a low-K+ solution, and it decreased in the presence of a high-K+ solution, compared with that measured in normal Krebs solution. Pinacidil consistently suppressed carbachol-induced depolarization of the membrane, with a reduction in the frequency of spontaneous action potentials. Glybenclamide (10(-6) M) did not inhibit the effect of pinacidil on increased action potential frequency induced by carbachol but blocked the membrane hyperpolarization induced by pinacidil (10(-5) M). In addition, the amplitude and maximum velocity of depolarization of carbachol- and current-induced action potentials were significantly decreased by pinacidil in the presence of glybenclamide. These results suggest that pinacidil blocks action potential generation in detrusor smooth muscle by inducing membrane hyperpolarization secondary to an increase in K+ permeability. Pinacidil, at high concentrations (> or = 10(-5) M), might block action potentials by inhibiting the voltage-sensitive Ca++ influx independently of hyperpolarization of the membrane. These mechanisms might be of benefit therapeutically in relaxation of unstable detrusor contractions.

Changes in electrical properties of guinea pig smooth muscle membrane by experimental bladder outflow obstruction.

The changes in membrane electrical properties of guinea pig bladder smooth muscle following experimental bladder outflow obstruction were studied by means of an intracellular microelectrode technique. The results of this study can be summarized as follows. 1) Bladder outflow obstruction resulted in a threefold increase in bladder weight after 4-8 wk. 2) The resting membrane potential was unchanged with obstruction; however, the obstructed smooth muscle membrane was more quiescent, with less spontaneous electrical activity compared with control tissue. 3) The membrane constants, space constant and time constant, were both reduced in the obstructed bladders. 4) There was no detectable difference in membrane depolarization induced by high extracellular K+ solution between control and obstructed bladders. 5) Both the membrane depolarization induced by K(+)-free solution or ouabain-containing Krebs solution and ouabain-sensitive membrane hyperpolarization by K(+)-containing solution after application of K(+)-free solution were significantly increased in the obstructed bladders. 6) Low extracellular Cl- solution evoked greater membrane depolarization in obstructed bladders. These results suggest that bladder outflow obstruction results in suppression of the cell-to-cell transfer of electrical activity and activation of a membrane electrogenic Na(+)-K+ pump mechanism in guinea pig detrusor.

Stretch-mediated visceral smooth muscle growth in vitro.

An in vitro model of smooth muscle stretch was developed to study mechanical stimulus as a possible mediator of visceral smooth muscle growth and differences in the growth response of smooth muscle from young and old animals. De novo DNA synthesis as measured by the aphidicolin-sensitive specific activity of DNA was used as an index of cell growth. Compared with old tissue, the rate of aphidicolin-sensitive DNA synthesis in smooth muscle from young animals was 3-5 and 1.5-2 times greater in bladder and taenia coli, respectively. Stretch of bladder muscle and taenia coli strips from young animals for 6 h increased the aphidicolin-sensitive specific activity of DNA 3-fold (P less than 0.01) and 1.5-fold (P less than 0.01), respectively. Tissue from old animals, however, under the same conditions increased the rate of aphidicolin-resistant DNA synthesis, possibly implying DNA repair. Autoradiography showed only labeled myocyte nuclei. These results indicate that homeostatic mechanisms modulating myocyte growth in visceral smooth muscle can respond to mechanical stimulus in the absence of other trophic factors.