Contemporary Outcomes of Surgery for Primary and Recurrent Genitourinary Fistulae in a Well-resourced Country.

BACKGROUND: Urinary fistula (UF) is a global health problem but less common in well-resourced countries. Over the past decade there has been a trend toward managing UF in dedicated centres. Most of the evidence for surgical treatment is from individual case series, with few publications that involve high numbers. We describe the repair of recurrent and complex UF cases and outcomes in a tertiary referral setting. OBJECTIVE: To describe UF aetiology, repair techniques, and outcomes. DESIGN SETTING AND PARTICIPANTS: This is a retrospective study of a series of patients undergoing UF repair at a specialist unit. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We describe the aetiology, cure rate, complications, and postoperative urinary incontinence rates for the series of UF cases. RESULTS AND LIMITATIONS: A consecutive series of 98 patients was identified, all of whom were tertiary referrals. Of these, 31 (31.6%) had at least one prior attempt at repair at another centre. The median age was 48 yr (interquartile range [IQR] 40-60.25). The median time from occurrence to repair was 12 mo (IQR 6-12). UF occurred most commonly following hysterectomy (48.0%), Caesarean section (9.2%), other gynaecological surgery (7.1%), and anti-incontinence surgery (7.1%). Complex fistulae (eg, repeat cases, radiation, ureteric involvement) comprised 41 of the cases (41.8%). Most patients with vesicovaginal fistula underwent repair via a transabdominal approach (70.4%). Tissue interposition was used in 96 cases (98%). There were no Clavien-Dindo grade >3 complications. Two patients (2%) had a persistent UF postoperatively. Two patients (2%) developed recurrence more than 2 yr after their initial repair, and both were successfully repaired at our centre. Twelve patients (12.3%) developed de novo overactive bladder, 22 (22.5%) developed stress urinary incontinence (13 had subsequent incontinence surgery), and two (2%) developed bladder pain (both had a subsequent cystectomy). CONCLUSIONS: Despite a high rate of recurrent and complex UF, successful lasting closure was achieved in 96% of our cases. A minority of patients developed other problems such as de novo overactive bladder and stress urinary incontinence that may require further treatment. PATIENT SUMMARY: Urinary fistula is an abnormal opening or connection in the urinary tract and is less common in well-resourced countries. As a consequence, management of this condition is more frequently undertaken at specialist units. Even patients with a complex fistula and those who have had multiple attempts at repair can experience a cure. Urinary leakage is a common complication after the operation but can be successfully managed with surgery.

Author Correction: Regenerative medicine and injection therapies in stress urinary incontinence.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Regenerative medicine and injection therapies in stress urinary incontinence.

Stress urinary incontinence (SUI) is a common and bothersome condition. Anti-incontinence surgery has high cure rates, but concerns about mesh tapes have resulted in the resurgence of surgical procedures that involve increased abdominopelvic dissection and morbidity. Injection therapy with urethral bulking agents or stem cell formulations have been developed as minimally invasive alternatives. Many synthetic and biological bulking agents have been trialled, but several have been discontinued owing to safety concerns. The use of Macroplastique and Contigen has the largest evidence base, but, overall, success rates seem to be similar between the various agents and positive outcomes are poorly sustained for more than 6 months. Furthermore, subjective cure rates, although initially high, also deteriorate over time. The available data consistently demonstrate manifestly poorer outcomes for injection therapies than for surgery. Stem cell treatments are thought to functionally regenerate the urethral sphincter in patients with suspected intrinsic sphincter deficiency. Autologous adipose and muscle-derived stem cells seem to be the intuitive cell source, as they are comparatively abundant, can be harvested and cause minimal donor site morbidity. To date, only a few small clinical studies have been reported and most data are derived from animal models. The success rates of stem cell injection therapies seem to be comparable with those of bulking agents.

Oestradiol-releasing Biodegradable Mesh Stimulates Collagen Production and Angiogenesis: An Approach to Improving Biomaterial Integration in Pelvic Floor Repair.

BACKGROUND: Polypropylene meshes cause severe complications in some patients. Materials that are biomechanically compatible and can better integrate into host tissues are urgently needed. OBJECTIVE: To design an oestradiol-releasing electrospun poly-l-lactic acid (PLA) mesh and evaluate its ability to stimulate new extracellular matrix and new blood vessel formation. DESIGN, SETTING, AND PARTICIPANTS: Human adipose derived mesenchymal cells (ADMSC) were isolated from fat. PLA meshes with micro- to nano-sized fibres containing 1%, 5%, and 10% oestradiol were constructed and used for in vitro and in vivo experiments. INTERVENTION: The angiogenic potential of the fibrous meshes was evaluated using an in vivo chorioallantoic membrane and an in vitro chick aortic arch assays. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Oestradiol release was measured fluorometrically. The effect of fibrous meshes on proliferation and extracellular matrix (ECM) production of ADMSC was assessed using immunohistology. Mechanical properties were tested using a tensiometer. RESULTS AND LIMITATIONS: The ultrastructure of the mesh was not affected by the inclusion of oestradiol and mechanical properties were only slightly modified. Oestradiol was released from PLA meshes over a 5-mo period. ADMSCs cultured on oestradiol-releasing PLA meshes produced more ECM involving collagen I, collagen III, and elastin. Oestradiol-releasing meshes doubled new blood vessel formation in the chorioallantoic membrane assay (p=0.001) and outgrowth of pro-angiogenic cells in the aortic arch assay (p=0.001). Further studies in longer-term animal models are required to confirm these results. CONCLUSIONS: Oestradiol-releasing PLA meshes increase ECM production and stimulate angiogenesis. As such, they are promising candidate materials to be used in pelvic floor repair and to improve the initial healing phase of a repair material following implantation. PATIENT SUMMARY: In this study, we designed a tissue engineered material to be used to support weakened pelvic floor tissues in women to avoid the complications associated with current surgical mesh. Our results showed that this material can stimulate new blood vessel formation in simple chick assays and tissue production in vitro. Both properties should help with the integration of this material into patients' tissues and merit further study in physiologically relevant animal models.

The choice of surgical approach in the treatment of vesico-vaginal fistulae.

Vesico-vaginal fistula is a global healthcare problem that has a high prevalence in sub-Saharan Africa, where obstetric complications lead to the development of this condition. Despite this, comparatively few fistula repairs are performed in well-resourced countries, where iatrogenic injury is the leading aetiological factor. As a consequence, much of our knowledge results from the experience of relatively few fistula surgeons in areas of high prevalence borne out of large case series or retrospective cohorts rather than high level evidence. At present, debate surrounds the exact timing of repair and the most appropriate surgical approach for this condition. Certain fistulae can be selected for conservative management, while those that do not demonstrate factors associated with spontaneous closure can be selected for surgery. Fistula surgeons should be aware of several potential repair options and the principles of contemporary fistula surgery, as the first attempt at repair is likely to be the best opportunity to achieve a successful outcome. We review the available literature and provide evidence on the optimal timing of repair, the appropriate surgical approach and the use of tissue interpositioning in fistula surgery.

The Midurethral Fascial "Sling on a String": An Alternative to Midurethral Synthetic Tapes in the Era of Mesh Complications.

BACKGROUND: Surgery for stress urinary incontinence (SUI) has been dominated recently by synthetic midurethral tapes. Increasing recognition of serious complications associated with nonabsorbable polypropylene mesh has led to resurgence in interest in alternative approaches, such as the autologous fascial sling (AFS). Despite being an efficacious and durable option in women with recurrent and complex SUI, there has been a reluctance to consider AFS in women with primary SUI due to a perception that it is only appropriate for treating patients with intrinsic sphincter deficiency (ISD) and is associated with high rates of urinary retention and de novo storage symptoms. OBJECTIVE: The video presented demonstrates the technique for a loosely applied midurethral AFS. In contrast to AFS applied at the bladder neck, this technical modification in patients who demonstrate primary SUI without ISD avoids high rates of de novo storage symptoms and urinary retention. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of data on patients undergoing AFS at a tertiary referral unit. SURGICAL PROCEDURE: AFS placement in a "loose" fashion using a short length of fascia suspended on a suture bilaterally at the midurethral level rather than at the bladder neck and only using more tension in patients with ISD. MEASUREMENTS: Subjective cure rate, rates of postoperative storage symptoms, and urinary retention necessitating intermittent self-catheterisation (ISC). RESULTS AND LIMITATIONS: A total of 106 patients underwent AFS; the mean follow-up period was 9 mo. The mean age was 52.6 (range 24-83) yr. In total, 46.2% had primary SUI, whilst all of the remaining 53.8% had undergone prior surgical intervention. Overall subjective cure occurred in 79.2% of patients; a further 15.1% described significant subjective improvement in symptoms, whilst 5.7% reported no change in symptoms. In those with primary SUI, rates of subjective cure, improvement, and nonresolution of symptoms were 87.8%, 12.2%, and 0%, respectively. In individuals with prior surgical intervention, rates of subjective cure, improvement, and nonresolution of symptoms were 72.0%, 17.5%, and 10.5%, respectively. De novo storage symptoms occurred in 8.2% of those with primary SUI compared with 14.0% of those with prior surgical intervention. Only 2.0% patients with primary SUI needed to perform ISC beyond 2 wk compared with 10.5% of those after prior surgery. CONCLUSIONS: A midurethral AFS appears to be effective and safe both in women with primary SUI who want to avoid the placement of permanent material and its attendant risks, and in more complex cases where this is less appropriate. PATIENT SUMMARY: A graft taken from the covering of the abdominal muscle or the outer aspect of the thigh is an alternative to a synthetic vaginal mesh in women who have stress urinary incontinence requiring surgical treatment. Placing the graft loosely at the midpoint of the urethral tube, rather than at the bladder neck, reduces the risk of postoperative voiding difficulty and overactive bladder symptoms. Long-term data have suggested an outcome at least as good as a synthetic nonabsorbable tape without the potential for sling erosion into adjacent structures, as it avoids the use of nonabsorbable material.

The Aetiology, Treatment, and Outcome of Urogenital Fistulae Managed in Well- and Low-resourced Countries: A Systematic Review.

CONTEXT: Urogenital fistula is a global healthcare problem, predominantly associated with obstetric complications in low-resourced countries and iatrogenic injury in well-resourced countries. Currently, the published evidence is of relatively low quality, mainly consisting retrospective case series. OBJECTIVE: We evaluated the available evidence for aetiology, intervention, and outcomes of urogenital fistulae worldwide. EVIDENCE ACQUISITION: We performed a systematic review of the PubMed and Scopus databases, classifying the evidence for fistula aetiology, repair techniques, and outcomes of surgery. Comparisons were made between fistulae treated in well-resourced countries and those in low-resourced countries. EVIDENCE SYNTHESIS: Over a 35-yr period, 49 articles were identified using our search criteria, which were included in the qualitative analysis. In well-resourced countries, 1710/2055 (83.2%) of fistulae occurred following surgery, whereas in low-resourced countries, 9902/10398 (95.2%) were associated with childbirth. Spontaneous closure can occur in up to 15% of cases using catheter drainage and conservative approaches are more likely to be successful for nonradiotherapy fistulae. Of patients undergoing repairs in well-resourced countries, the median overall closure rate was 94.6%, while in low-resourced countries, this was 87.0%. Closure was significantly more likely to be achieved using a transvaginal approach then a transabdominal technique (90.8% success vs 83.9%, Fisher's exact test; p=0.0176). CONCLUSIONS: It is difficult to conclude whether any specific route of surgery has advantage over any other, given the selection of patients to a particular procedure is based upon individual fistula characteristics. However, surgical repair should be carried out by experienced fistula surgeons, well versed in all techniques as the primary attempt at repair is likely to be the most successful. PATIENT SUMMARY: Urogenital fistulae are a common problem worldwide; however, the available evidence on fistula management is poor in quality. We searched the current literature and identified that 95% of fistulae occur following childbirth in low-resourced countries, whereas 80% of fistulae are associated with surgery in well-resourced countries, where successful repair is also more likely to be achieved. The first attempt at repair is often the most successful and therefore fistula surgery should be centralised to hospitals with the most experience.

Developing Repair Materials for Stress Urinary Incontinence to Withstand Dynamic Distension.

BACKGROUND: Polypropylene mesh used as a mid-urethral sling is associated with severe clinical complications in a significant minority of patients. Current in vitro mechanical testing shows that polypropylene responds inadequately to mechanical distension and is also poor at supporting cell proliferation. AIMS AND OBJECTIVES: Our objective therefore is to produce materials with more appropriate mechanical properties for use as a sling material but which can also support cell integration. METHODS: Scaffolds of two polyurethanes (PU), poly-L-lactic acid (PLA) and co-polymers of the two were produced by electrospinning. Mechanical properties of materials were assessed and compared to polypropylene. The interaction of adipose derived stem cells (ADSC) with the scaffolds was also assessed. Uniaxial tensiometry of scaffolds was performed before and after seven days of cyclical distension. Cell penetration (using DAPI and a fluorescent red cell tracker dye), viability (AlamarBlue assay) and total collagen production (Sirius red assay) were measured for ADSC cultured on scaffolds. RESULTS: Polypropylene was stronger than polyurethanes and PLA. However, polypropylene mesh deformed plastically after 7 days of sustained cyclical distention, while polyurethanes maintained their elasticity. Scaffolds of PU containing PLA were weaker and stiffer than PU or polypropylene but were significantly better than PU scaffolds alone at supporting ADSC. CONCLUSIONS: Therefore, prolonged mechanical distension in vitro causes polypropylene to fail. Materials with more appropriate mechanical properties for use as sling materials can be produced using PU. Combining PLA with PU greatly improves interaction of cells with this material.

Flexible cystourethroscopy in the follow-up of posturethroplasty patients and characterisation of recurrences.

BACKGROUND: Urethral strictures can be difficult to diagnose at an early stage because the urinary flow rate does not diminish until the urethral calibre is ≤3mm. In the past, posturethral surgery follow-up has relied upon flow rates and contrast imaging. OBJECTIVE: To evaluate the role of flexible urethroscopy in the follow-up of patients undergoing urethroplasty. DESIGN, SETTING, AND PARTICIPANTS: Prospective flexible urethroscopy follow-up of 144 male patients who underwent urethroplasty by a single surgeon over a 10-yr period at a tertiary referral centre. INTERVENTION: Flexible urethroscopy at 3, 6, and 12 mo postoperatively, and annually thereafter. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Type of recurrence, based on urethroscopy findings, and further interventions were measured. Actuarial analysis was performed using Kaplan-Meier curves and a log-rank test. RESULTS AND LIMITATIONS: All 144 patients underwent flexible urethroscopy follow-up over a median postoperative follow-up of 22 mo (range: 1-96 mo). No further intervention was required for 117 patients (81.25%); 27 (18.75%) developed recurrences that required further treatment. Recurrences included diaphragms (13 patients) or significant restenosis (14 patients). Diaphragms were treated by urethrotomy, gentle dilatation, or a short course of intermittent self-dilatation. Restenosis required repeated simple procedures or surgical revision. Most recurrences (26 of 27, 96%) were detected within the first year. Urinary peak flow-rate data were available for 11 of 27 of these recurrences; 7 patients had flow rates >15ml/s. Anastomotic procedures had greater success than augmentation urethroplasty (p=0.0136); there was no significant difference in outcomes between redo and non-redo surgery (p=0.2093) CONCLUSIONS: Endoscopic follow-up of patients after urethroplasty enables earlier identification and treatment of recurrences compared to the use of urinary flow rates alone. It also enables the identification of two different morphologic recurrence patterns that require different types of intervention. PATIENT SUMMARY: Endoscopy detects most stricture recurrences within 1 yr after urethroplasty and is more sensitive than using urinary flow rates alone.

Current trends in urethral stricture management.

The recent International Consultation on Urological Disease (ICUD) panel 2010 confirmed that a urethral stricture is defined as a narrowing of the urethra consequent upon ischaemic spongiofibrosis, as distinct from sphincter stenoses and a urethral disruption injury. Whenever possible, an anastomotic urethroplasty should be performed because of the higher success rate as compared to augmentation urethroplasty. There is some debate currently regarding the critical stricture length at which an anastomotic procedure can be used, but clearly the extent of the spongiofibrosis and individual anatomical factors (the length of the penis and urethra) are important, the limitation for this being extension of dissection beyond the peno-scrotal junction and the subsequent production of chordee. More recently, there has been interest in whether to excise and anastomose or to carry out a stricturotomy and reanastomosis using a Heineke-Miculicz technique. Augmentation urethroplasty has evolved towards the more extensive use of oral mucosa grafts as compared to penile skin flaps, as both flaps and grafts have similar efficacy and certainly the use of either dorsal or ventral positioning seems to provide comparable results. It is important that the reconstructive surgeon is well versed in the full range of available repair techniques, as no single method is suitable for all cases and will enable the management of any unexpected anatomical findings discovered intra-operatively.

Recent developments in technology for the assessment and management of incontinence.

Urinary incontinence, the leakage of urine, is a common condition, which can have a significant impact on a patient's quality-of-life. Incontinence may arise as a consequence of a weakness of the urinary sphincter or bladder dysfunction, usually over-activity. Incontinence therapies occupy a large proportion of the healthcare budget. As no single device to manage incontinence is appropriate for all situations, a diverse range of products are available on the market and the development of improved products based on fundamental designs has been slow. This review highlights some of the key issues of continence care and describes the current technology and recent developments involved in the diagnosis, assessment and treatment of incontinence, along with the strengths and limitations of these methods. These issues are imperative to address if improved technology is to be developed.