Advances toward tissue engineering for the treatment of stress urinary incontinence

Suburethral pubovaginal sling placement is a common surgical procedure for the treatment of stress urinary incontinence. A wide variety of graft materials is available, each associated with inherent desirable and undesirable characteristics and complications. In this article, we discuss the rationale for and application of small intestinal submucosa (SIS) in lower urinary tract tissue engineering, with emphasis on the use of SIS as a suitable and biologically compatible sling material. In addition, we discuss exciting research regarding the engineering of true functional sphincter reconstruction using this biologic scaffold and pre-seeded muscle cells.     

经耻骨上膀胱尿道悬吊术的手术护理

目的:探讨经耻骨上膀胱尿道悬吊术(SPARC)的手术护理方法。方法:对24例女性尿失禁采用SPARC进行手术治疗。结果:21例患者术后尿控满意,3例有轻度尿失禁,无排尿困难及尿路感染。结论:做好术前宣教、心理护理、熟悉手术步骤、对手术所需器械和物品的充分准备是保证手术顺利实施的前提。注意患者体位的护理,预防并发症的发生,熟练准确的技术配合是SPARC手术的护理核心。     

Advances in the understanding of sress urinary incontinence and the promise of stem-cell therapy

The middle urethra and external urethral sphincter are the focus in management of stress urinary incontinence, and recent cellular-therapy research suggests a new paradigm in treatment. Cell-based therapies are most often described as using autologous multipotent stem cells procured from bone marrow in procedures that may be painful, require anesthesia, and yield low numbers of mesenchymal stem cells upon processing. In contrast, muscleand adipose-derived stem cells can be obtained easily in large quantities under local anesthesia. Instead of lifting the urethra with a sling or bulking up the urethral sphincter with collagen, we now have the potential to restore function with the use of autologous stem cells.     

Conservative Treatment for Postprostatectomy Incontinence

Postprostatectomy incontinence (PPI) is a bothersome complication of radical prostatectomy. Although most men recover from PPI, some men continue to have persistent urinary incontinence. The initial management of persistent PPI usually consists of conservative measures such as pelvic floor muscle exercises. Surgical treatments are usually not entertained for men with urinary incontinence until conservative treatments have failed. This article discusses risk factors for PPI and various options for its treatment, including biofeedback and pharmacotherapy.Key words: Postprostatectomy incontinence, Radical prostatectomy, Pelvic floor muscle training, Pelvic floor stimulationPostprostatectomy incontinence (PPI) is a bothersome complication of radical prostatectomy (RP). Although most men recover from PPI, some men continue to have persistent urinary incontinence and roughly half of these men seek treatment.¹ It is important to understand the natural history of postprostatectomy urinary dysfunction prior to initiating treatment. Generally, the initial management of persistent PPI consists of conservative measures such as pelvic floor muscle exercises.     

A components analysis of biofeedback in the treatment of fecal incontinence

Fecal incontinence is a socially disabling symptom for which rectosphincteric biofeedback has been reported to be dramatically effective. The most commonly employed biofeedback procedure incorporates three separate and potentially effective components: (1) exercise of the external sphincter muscle, (2) training in discrimination of rectal sensations, and (3) training synchrony of the internal and external sphincter responses. This paper reports the results of single case experiments employed with eight incontinent patients to examine the contributions of each of these components. All eight patients improved, but only one required the biofeedback procedure as it was originally described. Three responded to sensory discrimination training, one to exercise training, and one to the training of synchronous sphincteric responses; three recovered independently of the effects of biofeedback. Despite the achievement of continence, the rectosphincteric reflexes following treatment continued to be abnormal in every case. These findings suggest that the character of the external sphincter response to rectal distension is an unreliable index of sphincter function and that exercise and sensory discrimination training procedures are effective for some cases of fecal incontinence.The work described in this paper was supported by Grant No. MA 6241 from the Medical Research Council of Canada.     

Subcutaneous mastectomy. The excess skin problem.

Subcantaneous mastectomy through a lateral approach, with preservation of the nipple and areola on a dermal pedicle, removing the excess skin at the time of aubautaneous mastectomy, is a safe procedure which results in esthetically acceptable breasts. The surgical approach greatly facilitates the removal of the entire glandular portion of the breast. The need for a second surgical procedure is eliminated. Lateral biopsy scars can be reinforced by the dermal sling support, thereby decreasing the chances of exposure of the implant. The implant is also successfully and easily held in position by the use of the dermal-fat sling support. The nipple and areola survive quite well on the dermal pedicle, with preservation of contractility and sensation, as well as of blood supply.     

Biofeedback in treatment of urinary incontinence in stroke patients

Urinary incontinence can occur poststroke owing to weakness or incoordination of sphincter muscles, impaired bladder sensation, or hyperreflexic, neurogenic bladder. Four male subjects who had urinary incontinence associated with a stroke that had occurred 8 months to 10 years earlier, and who averaged 1.6 to 7.5 accidental voidings per week, participated in an outpatient study with a 4-week scheduled-voiding baseline, 2 to 5 sessions of biofeedback-assisted bladder retraining, and 6- to 12-month follow-up. Training sessions included stepwise filling of the bladder and manometric feedback display of bladder pressure, abdominal pressure, and external anal sphincter pressure. Training procedures were designed to teach subjects to attend to bladder sensations, inhibit bladder contractions, and improve voluntary sphincter muscle control. All four subjects achieved and maintained continence regardless of substantial differences in subject characteristics, including laterality of stroke, degree of sensory impairment, and independence in daily activities.     

Biofeedback in treatment of urinary incontinence in stroke patients

Urinary incontinence can occur poststroke owing to weakness or incoordination of sphincter muscles, impaired bladder sensation, or hyperreflexic, neurogenic bladder. Four male subjects who had urinary incontinence associated with a stroke that had occurred 8 months to 10 years earlier, and who averaged 1.6 to 7.5 accidental voidings per week, participated in an outpatient study with a 4-week scheduled-voiding baseline, 2 to 5 sessions of biofeedback-assisted bladder retraining, and 6- to 12-month follow-up. Training sessions included stepwise filling of the bladder and manometric feedback display of bladder pressure, abdominal pressure, and external anal sphincter pressure. Training procedures were designed to teach subjects to attend to bladder sensations, inhibit bladder contractions, and improve voluntary sphincter muscle control. All four subjects achieved and maintained continence regardless of substantial differences in subject characteristics, including laterality of stroke, degree of sensory impairment, and independence in daily activities.     

Mechanics of the urethral duct: tissue constitutive formulation and structural modeling for the investigation of lumen occlusion

Urinary incontinence, often related to sphincter damage, is found in male patients, leading to a miserable quality of life and to huge costs for the healthcare system. The most effective surgical solution currently considered for men is the artificial urinary sphincter that exerts a pressure field on the urethra, occluding the duct. The evaluation of this device is currently based on clinical and surgical competences. The artificial sphincter design and mechanical action can be investigated by a biomechanical model of the urethra under occlusion, evaluating the interaction between tissues and prosthesis. A specific computational approach to urethral mechanics is here proposed, recalling the results of previous biomechanical experimental investigation. In this preliminary analysis, the horse urethra is considered, in the light of a significant correlation with human and in consideration of the relevant difficulty to get to human samples, which anyway represents the future advance. Histological data processing allow for the definition of a virtual and a subsequent finite element model of a urethral section. A specific hyperelastic formulation is developed to characterize the nonlinear mechanical behavior. The inverse analysis of tensile tests on urethra samples leads to the definition of preliminary constitutive parameters. The parameters are further refined by the computational analysis of inflation tests carried out on the entire urethral structure. The results obtained represent, in the light of the correlation reported, a valid preliminary support for the information to be assumed for prosthesis design, integrating surgical and biomechanical competences.     

Sphincter incontinence: Is regenerative medicine the best alternative to restore urinary or anal sphincter function?

Incontinence is a major public health concern in aging societies. It is caused by age-dependent spontaneous apoptosis of muscle cells in the urinary and fecal sphincters, and is aggravated in women due to birth trauma. Compared to other currently employed invasive surgical management techniques associated with morbidity and recurrence, replacement or regeneration of dysfunctional sphincter through stem cell therapy and tissue engineering techniques hold great promise. This review focuses on the pathophysiological analysis of urinary incontinence and the possible application of muscle-derived-stem cells, satellite cells, chondrocytes and adipose-derived-stem cells in restoring sphincter functions.     

Dynamic rectus abdominis muscle sphincter for stoma continence: an acute functional study in a dog model

Fecal stomal incontinence is a problem that continues to defy surgical treatment. Previous attempts to create continent stomas using dynamic myoplasty have had limited success due to denervation atrophy of the muscle flap used in the creation of the sphincter and because of muscle fatigue resulting from continuous electrical stimulation. To address the problem of denervation atrophy, a stomal sphincter was designed using the most caudal segment of the rectus abdominis muscle, preserving its intercostal innervation as well as its vascular supply. The purpose of the present study was to determine whether this rectus abdominis muscle island flap sphincter design could maintain stomal continence acutely. In this experiment, six dogs were used to create eight rectus abdominis island flap stoma sphincters around a segment of distal ileum. Initially, the intraluminal stomal pressures generated by the sphincter using different stimulation frequencies were determined. The ability of this stomal sphincter to generate continence at different intraluminal bowel pressures was then assessed. In all cases, the rectus abdominis muscle sphincter generated peak pressures well above those needed to maintain stomal continence (60 mmHg). In addition, each sphincter was able to maintain stomal continence at all intraluminal bowel pressures tested.     

Surgical treatment of submucous cleft palate: a comparative trial of two modalities for palatal closure

Submucous cleft palate is a congenital malformation with specific clinical and anatomical features. It can be present with or without velopharyngeal insufficiency. Surgical treatment of this malformation is indicated only when velopharyngeal insufficiency has been demonstrated. This article compares two modalities of surgical treatment for submucous cleft palate. The first includes a minimal incision palatopharyngoplasty, as described in a previous report. The second combines the first technique with additional individualized velopharyngeal surgery (individualized pharyngeal flap or sphincter pharyngoplasty) performed simultaneously. The individualized part of the procedure was selected and performed according to the findings of videonasopharyngoscopy and multiview videofluoroscopy, as reported previously. Two hundred and three patients with submucous cleft palate were studied from 1990 to 1999. Videonasopharyngoscopy and multiview videofluoroscopy demonstrated velopharyngeal insufficiency in 72 patients, who were randomly divided into two groups. Those in group 1 (n = 37) underwent a minimal incision palatopharyngoplasty. Patients in group 2 (n = 35) also underwent that procedure but simultaneously received individualized pharyngeal flap or sphincter pharyngoplasty, according to the findings of videonasopharyngoscopy and multiview videofluoroscopy. The median age of the patients from both groups was not significantly different (p > 0.5). The frequency of residual velopharyngeal insufficiency after palatal closure was not significantly different in both groups of patients (14 percent versus 11 percent; p > 0.5). The mean size of the gap at the velopharyngeal sphincter during speech was not significantly different in both groups of patients before surgery (23 percent versus 22 percent; p > 0.5). After the surgical procedures, there was a nonsignificant difference between both groups of patients in mean residual size of the gap in cases of velopharyngeal insufficiency (7 percent versus 8 percent; p > 0.5). It seems that minimal incision palatopharyngoplasty is a safe and reliable procedure for palatal closure in patients with submucous cleft palate. The use of additional individualized velopharyngeal surgery performed simultaneously did not seem to decrease the frequency of residual velopharyngeal insufficiency. Moreover, the residual size of the gap at the velopharyngeal sphincter was not significantly reduced when an additional surgical procedure was performed simultaneously with palatal closure.     

Feline lower esophageal sphincter sling and circular muscles have different functional inhibitory neuronal responses

The lower esophageal sphincter (LES) has a circular muscle component exhibiting spontaneous tone that is relaxed by nitric oxide (NO) and a low-tone sling muscle that contracts vigorously to cholinergic stimulation but with little or no evidence of NO responsiveness. This study dissected the responses of the sling muscle to nitrergic innervation in relationship to its cholinergic innervation and circular muscle responses. Motor responses were induced by electrical field stimulation (EFS; 1-30 Hz) of muscle strips from sling and circular regions of the feline LES in the presence of cholinergic receptor inhibition (atropine) or NO synthase inhibition [NG-nitro-L-arginine (L-NNA)+/-atropine]. This study showed the following. First, sling muscle developed less intrinsic resting tone compared with circular muscle. Second, with EFS, sling muscle contracted (most at 50% by 5 Hz. Third, on neural blockade with atropine or L-NNA+/-atropine, 1) sling muscle, although predominantly influenced by excitatory cholinergic stimulation, had a small neural NO-mediated inhibition, with no significant non-NO-mediated inhibition and 2) circular muscle, although little affected by cholinergic influence, underwent relaxation predominantly by neural release of NO and some non-NO inhibitory influence (at higher EFS frequency). Fourth, the sling, precontracted with bethanecol, could relax with NO and some non-NO inhibition. Finally, the tension range of both muscles is similar. In conclusion, sling muscle has limited NO-mediated inhibition to potentially augment or replace sling relaxation effected by switching off its cholinergic excitation. Differences within the LES sling and circular muscles could provide new directions for therapy of LES disorders.     

Regional differences in L-type Ca2+ channel expression in feline lower esophageal sphincter

In humans and cats, muscle from the lower esophageal sphincter (LES) circular region exhibits greater spontaneous tone than LES sling muscle, whereas the sling muscle is much more responsive to cholinergic stimulation. Despite physiological and pharmacological evidence for the presence of L-type Ca2+ channel current (ICa,L) activity in LES circular muscle, the identity of this channel has not been demonstrated biochemically or electrophysiologically fingerprinted. Furthermore, there is no information on the channel's presence and role in the sling region of the LES. We hypothesized that regional differences in the expression of ICa,L between LES circular and sling muscles, if present, could contribute to the functional asymmetry observed within the LES. ICa,L expression was compared between circular and sling regions of the LES by Western blot analysis. The patch-clamp technique was used to study ICa,L. Muscle strip studies assessed ICa,L contribution to contractile activity. We found both protein expression of ICa,L and ICa,L density to be greater in LES circular muscle than sling muscle. ICa,L voltage- and time-dependent activation and inactivation curves were similar in cells from both regions. ICa,L blockade with nifedipine inhibited spontaneous tone and ACh-induced contractions only in circular muscle but was able to abolish depolarization (KCl)-induced contractions in both sling and circular muscles. In contrast, La3+ inhibited tone and ACh-induced contractions in muscles from both regions. Therefore, regional myogenic differences in ICa,L expression within the LES circular and sling muscle exist and provide one explanation for the differential contribution of sling and circular muscle to LES contractility.     

Potassium channel diversity within the muscular components of the feline lower esophageal sphincter

We hypothesized that regional differences in electrophysiological properties exist within the musculature of the feline lower esophageal sphincter (LES) and that they may potentially contribute to functional asymmetry within the LES. Freshly isolated esophageal smooth muscle cells (SMCs) from the circular muscle and sling regions within the LES were studied under a patch clamp. The resting membrane potential (RMP) of the circular SMCs was significantly more depolarized than was the RMP of the sling SMCs, resulting from a higher Na+ and Cl- permeability in circular muscle than in sling muscle. Large conductance Ca2+-activated K+ (BKCa) set the RMP at both levels, since specific BKCa inhibitors caused depolarization; however, BKCa density was greatest in the circular region. A significant portion of the outward current was due to non-BKCa, especially in sling muscle, and likely delayed rectifier K+ channels (KDR). There was a large reduction in outward current with 4-aminopyridine (4-AP) in sling muscle, while BKCa blockers had a limited effect on the voltage-activated outward current in sling muscle. Differences in BKCa:KDR channel ratios were also manifest by a leftward shift in the voltage-dependent activation curve in circular cells compared to sling cells. The electrophysiological differences seen between the circular and sling muscles provide a basis for their different contributions to LES activities such as resting tone and neurotransmitter responsiveness, and in turn could impart asymmetric drug responses and provide specific therapeutic targets.     

The frequency of 'atypia of undetermined significance' interpretations for thyroid fine-needle aspirations is negatively correlated with histologically proven malignant outcomes

Objective: Cytopathologists' usage patterns for 'atypia of undetermined significance' (AUS) in thyroid fine-needle aspiration (FNA) are not well understood. AUS rates over a 5-year period were analyzed to quantify variability and identify correlations with experience and histologic outcomes. Study Design: A retrospective review of thyroid FNAs from a tertiary-care hospital from 2005 to 2009 was performed. Results were compiled for individual cytopathologists, stratified by year, and correlated with histologic outcomes. Results: Thyroid FNAs (5,327) were evaluated by 7 cytopathologists, with an overall AUS rate of 11.2%. The annual AUS rate remained relatively constant over this time period, though notable inter- and intrapathologist variability was seen. The AUS rate was significantly lower for those with cytopathology boards (10.3%) compared to those without (14.0%). There was no correlation between the AUS rate and cytopathologist experience or thyroid FNA volume. The AUS rate and malignant outcome were inversely related: the higher an individual's AUS rate was, the lower the rate of malignancy for that AUS cohort was. Conclusions: Individual cytopathologist AUS rates were variable and often exceeded the recommended target of 7%. The application of recently published defined diagnostic criteria, along with directed cytopathologist feedback, may reduce observer variability and appropriately lower AUS utilization.     

Velopharyngeal motion after sphincter pharyngoplasty: a videonasopharyngoscopic and electromyographic study

Sphincter pharyngoplasty is a surgical procedure for managing velopharyngeal insufficiency after palatal closure. This procedure is intended to create an active diaphragm for velopharyngeal closure. The purpose of this study was to evaluate velopharyngeal motion after sphincter pharyngoplasty, by using selective electromyography and simultaneous videonasopharyngoscopy. Twenty-five patients who were subjected to sphincter pharyngoplasty from 1985 to 1996 were reviewed. All conditions were evaluated by using electromyography with simultaneous videonasopharyngoscopy. The following velopharyngeal muscles were examined: superior constrictor pharyngeus, palatopharyngeus, and levator veli palatini. The palatopharyngeus was included in the superiorly based surgical flaps inserted at the posterior pharyngeal wall. Twenty-three patients (92 percent) showed complete velopharyngeal closure. The two patients with residual velopharyngeal insufficiency showed a defect size of 20 and 25 percent. None of the patients showed electromyographic activity at the superiorly based flaps, indicating absence of activity of the palatopharyngeus muscles. However, all patients showed normal electromyographic activity at the superior constrictor pharyngeus and the levator veli palatini. Videonasopharyngoscopy demonstrated that lateral pharyngeal wall movements, which ranged from 25 to 40 percent, were related to strong electromyographic activity at the superior constrictor pharyngeus. It is concluded that the superiorly based pharyngeal flaps of the sphincter pharyngoplasty do not seem to create an active diaphragm for velopharyngeal closure. Moreover, the observed sphinctering seems to be passive, caused by the contraction of the superior constrictor pharyngeus.     

The prevalence of urinary incontinence

Urinary incontinence is a significant health problem with considerable social and economic impact. It is important to distinguish between prevalence and incidence with regard to incontinence, and prevalence-the probability of having incontinence within a defined population at a defined point in time-is the more important when considering its impact and the utilization of healthcare resources. There are large variations in the severity and impact of incontinence, and its severity, frequency, and predictability all need to be considered when evaluating its effects on patients, The degree of bother is particularly significant when determining who will need treatment. Incontinence may be a result of bladder dysfunction, sphincter dysfunction, or a combination of both, but large-scale studies are not designed to determine the etiology. In young women, the prevalence of incontinence is usually low, but prevalence peaks around menopause, with a steady rise there-after into later life. Although the prevalence of stress and mixed (stress and urge) incontinence is higher than urge incontinence, the latter is more likely to require treatment. In women, moderate and severe bother have a prevalence ranging from about 3% to 17%. Severe incontinence has a low prevalence in young women, but rapidly increases at ages 70 through 80. In men, the prevalence of incontinence is much lower than in women, about 3% to 11% overall, with urge incontinence accounting for 40% to 80% of all male patients. Stress incontinence accounts for less than 10% of cases and is attributable to prostate surgery, trauma, or neurological injury. Incontinence in men also increases with age, but severe incontinence in 70- to 80-year-old men is about half of that in women. The most effective therapy for incontinence will rely on targeting the correct populations to be treated, which depends on how data is collected on prevalence and severity.     

Treatment of stress urinary incontinence with duloxetine hydrochloride

Currently, there are no approved medications for the treatment of stress urinary incontinence (SUI) in the United States. The effectiveness of duloxetine in the treatment of SUI is linked to its inhibition of presynaptic neuronal reuptake of serotonin and norepinephrine in the central nervous system, resulting in elevated levels of serotonin and norepinephrine in the synaptic cleft. In animal studies, this agent leads to an increase in nerve stimulation to the urethral striated sphincter muscle. A similar mechanism in women is believed to result in stronger urethral contractions, with improved sphincter tone during urine storage and physical stress. In 3 randomized, placebo-controlled clinical trials, patients receiving duloxetine had a statistically significant and clinically relevant reduction in the number of incontinence episodes and a corresponding improvement in quality of life. If this use of duloxetine is approved by the U.S. Food and Drug Administration, as it has been by the European regulatory agencies, it will be the first drug indicated for the treatment of SUI. This pharmacologic therapy is an additional option for women and is likely to become an integral component of patient management.