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.

Electrical and mechanical responses of guinea-pig bladder muscle to nerve stimulation.

1 The electrical and mechanical responses to transmural stimulation of intrinsic nerves have been recorded from smooth muscle strips dissected from the dome of the guinea-pig bladder, by use of intracellular microelectrodes, and conventional tension recording techniques. 2 Stimulation of intrinsic nerves evoked action potentials in all cells studied. Hyperpolarization of the cells by extracellular current injection revealed subthreshold excitatory junction potentials (e.j.ps) in about a quarter of the cells studied. 3 Action potentials could still be evoked in the presence of atropine and neostigmine, but were abolished after desensitization of the cells to alpha, beta-methylene ATP, a stable analogue of ATP. 4 In the presence of neostigmine, the evoked action potential was followed by a slow depolarization of the membrane. The mechanical response increased in amplitude and duration. 5 The contractile response to transmural nerve stimulation was reduced but not abolished in the presence of either atropine or desensitizing doses of alpha, beta-methylene ATP. Atropine was more effective at high frequencies of stimulation (greater than or equal to 30 Hz), and alpha, beta-methylene ATP at low frequencies (less than or equal to 15 Hz). In combination the drugs abolished the response. 6 The results suggest that the mechanical response to excitatory nerve stimulation is biphasic. The early transient response is elicited by e.j.ps and evoked spikes, is resistant to atropine, but sensitive to desensitization of purinoceptors. The late response is mediated through muscarinic receptors, involves little membrane depolarization, and is unaffected by desensitization of purinoceptors. These responses are analogous to the responses seen in rabbit bladder, and in the sympathetically innervated rat tail artery and guinea-pig vas deferens.

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.

Current concepts of female pelvic anatomy and physiology.

The female urinary bladder and urethra are situated on the intrapelvic surface of the anterior vaginal wall, firmly anchored to the distal vagina by the urogenital diaphragm and to the superior vagina at the vesicocervicouterine junction. The anterior surface of the proximal urethra is firmly anchored to the posterior aspect of the symphysis pubis by the pubourethral ligaments and to the remaining distal vagina by the lower two thirds of the urogenital diaphragm. The lateral bladder wall derives its support from the anterior vaginal wall attachments to the pelvic sidewall. The anterior vaginal wall is strongly supported by pubococcygeus muscle fibers inserting on the vaginal wall and the genital hiatus and by the cardinal and uterosacral ligaments. Vaginal detachment from the lateral pelvic sidewall can result in herniation, with accompanying secondary posterior bladder descent. Levator ani weakness or injury may be a contributing etiologic factor in the genesis of vaginal wall detachment and the development of stress incontinence.

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.

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.

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.

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.

Receptor operated intracellular calcium stores in the smooth muscle of the guinea pig bladder.

Study of the in vitro behavior of strips of guinea pig bladder and taenia coli demonstrated that: Both bladder and taenia temporarily retain their ability to contract in Ca-free solutions, but the magnitude of this response decays with time. Carbachol is capable of producing contraction in Ca-free solution for a longer period of time than K depolarisation. Once lost, the ability of carbachol (but not K) to contract the tissues in Ca-free solution can be temporarily restored by a brief application of high Ca. The size of the carbachol contraction in Ca-free solution is reduced in Na-free solution, suggesting that membrane-bound Ca may not play a major role in this response. In depolarised bladder exposed to nifedipine 2 X 10(-7) M, carbachol can only elicit 1 large contraction, suggesting depletion of an intracellular source. It is concluded that whereas the response of the bladder to depolarisation depends primarily on extracellular Ca, the response to carbachol may also involve release of stored Ca and that the bladder, like other smooth muscles, appears to contain agonist-releasable intracellular Ca stores.

The action potential of guinea pig bladder smooth muscle.

The smooth muscle of the guinea pig bladder demonstrates in vitro spontaneous electrical activity in the form of action potentials which are associated with contraction. The action potential frequency is highly voltage-sensitive. The relative contributions of Na, Ca and K to the action potential elicited by depolarizing current have been studied using intracellular microelectrodes. In solutions in which NaCl is replaced by sucrose, the membrane hyperpolarizes and the rate of rise and after-hyperpolarization of the elicited action potential is increased. The amplitude is unaffected. In Ca-deficient solutions, the membrane depolarizes, the rate of rise and amplitude of the action potential is reduced, and the after-hyperpolarization is decreased. Nifedipine reduces amplitude and rate of rise but does not affect after-hyperpolarization. In the presence of the K-channel antagonist TEA, the duration of the action potential is prolonged, but the amplitude and rate of rise are unaffected. After-hyperpolarization is not reduced. It is concluded that the action potential of guinea pig bladder muscle, like many other smooth muscles studied, is Ca-based. Repolarization depends on changes in K conductance. The after-hyperpolarization is voltage-sensitive.

Radical prostatectomy and cystoprostatectomy with preservation of potency. Results using a new nerve-sparing technique.

A surgical technique that preserves the branches of the pelvic plexus that innervate the corpora cavernosa was employed during radical retropubic prostatectomy in 64 men and radical cystoprostatectomy in 11 men. In patients undergoing radical retropubic prostatectomy, sexual function returned gradually in the vast majority of patients post-operatively and by 1 year 86% were potent. The age of the patient did not influence post-operative potency but potency did correlate with clinical and pathological stage. Preliminary data suggest that deliberate excision of the neurovascular bundle unilaterally did not adversely affect potency. Of the 11 patients who underwent radical cystoprostatectomy, 82% have erections. Of the 6 patients with sexual partners who have been followed for 1 year, 4 (67%) are potent. These data suggest that erectile function can be preserved in most patients following radical prostatectomy and cystoprostatectomy.

Cyst of the ejaculatory duct/urogenital sinus.

We report a case of a midline cyst involving both ejaculatory ducts and seminal vesicles. There have been only 3 previous reports in the literature of ejaculatory duct cysts, 1 of which was iatrogenic, and all have been unilateral. However, several cases have been reported of cysts arising from the müllerian duct or seminal vesicle, in which the described anatomy is essentially identical to our case. It is proposed that midline retroprostatic/retrovesical cysts that communicate with both wolffian systems be classified as urogenital sinus cysts.

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.

Intracorporeal pressure monitoring during artificial penile erection.

In an effort to determine if artificial penile erection has any harmful effect in children intracorporeal pressures were measured in 12 boys (mean age 18 months) with mid shaft hypospadias. Using a solid state intracompartmental pressure monitoring system, intracorporeal pressures were obtained during full penile erection and after removal of the tourniquet at detumescence. The mean intracorporeal pressure obtained was 85.9 mm. Hg during erection and 21.6 mm. Hg at detumescence. The systemic arterial pressure obtained was 102 mm. Hg at full erection. The pressure studies would suggest that the intracorporeal pressures achieved during full artificial erection would not be harmful to the cavernosal tissue in the hypospadiac child.

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.

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)

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.

Analysis of the detrusor smooth muscle action potential.

A method is described to record bladder smooth muscle action potential (AP) data and subsequently in digitized form analyze the constitutive elements of the AP. Manipulation of digitized data can give accurate descriptive information on the AP configuration and kinetics. In the future this type of analysis will hopefully lead to more precise, quantitative information on changes in the smooth muscle AP kinetics with disease states and facilitate a clearer understanding of the pathophysiological processes underlying changes in detrusor contractility.

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.