Christopher Hillary

Tissue engineered buccal mucosa for urethroplasty: Progress and future directions

PURPOSE Autologous buccal mucosa is commonly utilized in the surgical treatment of urethral strictures. Extensive strictures require a larger quantity of tissue, which may lead to donor site morbidity. This review assesses progress in producing tissue engineered buccal mucosa as an alternative graft material. RESULTS Few clinical studies have introduced cells onto biological or synthetic scaffolds and implanted resulting constructs in patients. The available studies show that buccal mucosa cells on acellular human dermis or on collagen matrix lead to good acute stage tissue integration. Urothelial cells on a synthetic substrate also perform well. However while some patients do well many years post-grafting, others develop stricture recurrence. Acellular biomaterials used to treat long urethral defects in animals commonly lead to fibrosis. CONCLUSIONS Tissue engineered buccal mucosa shows promise as a substitute for native tissue. The fibrosis which occurs months post-implantation may reflect the underlying disease process recurring in these patients.

Evaluating Alternative Materials for the Treatment of Stress Urinary Incontinence and Pelvic Organ Prolapse: A Comparison of the In Vivo Response to Meshes Implanted in Rabbits.

PURPOSE Serious complications can develop with the mesh implants used for stress urinary incontinence and pelvic organ prolapse surgery. We evaluated 2 materials currently in clinical use and 2 alternative materials using a rabbit abdominal model to assess host response and biomechanical properties of the materials before and after implantation. MATERIALS AND METHODS Poly-L-lactic acid and polyurethane meshes were electrospun to be compared to commercially available polypropylene and polyvinylidene fluoride meshes. A total of 40 immunocompetent full-thickness abdominal wall defect rabbit models were used, including 8 in each of the poly-L-lactic acid, polyurethane, polyvinylidene fluoride and polypropylene experimental groups, and sham controls. Two 20 mm defects were created per animal and primarily repaired. The experimental groups then underwent onlay of each repair material while sham controls did not. Four rabbits per group were sacrificed at days 30 and 90. Abdominal wall specimens containing the defect with or without repair material were explanted to be assessed by histology (hematoxylin and eosin staining, and immunohistochemistry) and biomechanical testing at 30 and 90 days. RESULTS At 90 days of implantation tissues repaired with all 4 materials showed biomechanical properties without significant differences. However, polypropylene and polyvinylidene fluoride meshes demonstrated a sustained chronic inflammatory response profile by 90 days. In contrast, poly-L-lactic acid and polyurethane meshes integrated well into host tissues with a decreased inflammatory response, indicative of constructive remodeling. CONCLUSIONS Poly-L-lactic acid and polyurethane alternative materials achieved better host integration in rabbit models than current synthetic repair materials.

Qualitative Exploration of the Patient Experience of Underactive Bladder

BACKGROUND Underactive bladder (UAB) is considered the symptom complex associated with the urodynamic diagnosis of detrusor underactivity. OBJECTIVE The aim of this research was to investigate the patient reported experience of the symptoms, signs, and impact of UAB. This research is also part of the initial qualitative phase for the development of a new patient reported outcome measure for the assessment of UAB. DESIGN, SETTING, AND PARTICIPANTS Qualitative methods were used to understand the experience of UAB from a patient perspective, in a purposive sample of male (n=29) and female (n=15) patients aged 27-88 yr (mean: 64 yr), diagnosed with a primary diagnosis of detrusor underactivity, with or without coexisting urological conditions. Semistructured interviews were conducted in Bristol, UK. RESULTS Male and female patients reported a variety of lower urinary tract symptoms and associated impact on quality of life. Storage symptoms of nocturia, increased daytime frequency, and urgency, and the voiding symptoms of slow stream, hesitancy, and straining were reported by over half of the patients. A sensation of incomplete emptying and postmicturition dribble were also frequently described. Most had a post void residual >30ml (n=34, 77%, median: 199ml) with many reporting urinary tract infections, a history of self-catheterisation, and some experiencing occasional acute retention episodes. These symptoms and signs can have a broad impact on quality of life including having to plan their daily activities around the location of toilets, disruption to sleep, social life, and associated effect on family and friends. CONCLUSIONS Knowledge of the lived experience of UAB obtained in the current study will be used for the development of a new patient reported outcome measure and help inform the current working definition of UAB. PATIENT SUMMARY The symptoms, signs, and impact on quality of life of underactive bladder are described by patients with the condition.

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%, Fishers 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.

Application of Tissue Engineering to Pelvic Organ Prolapse and Stress Urinary Incontinence.

Synthetic or biological materials can be used for the surgical repair of pelvic organ prolapse (POP) or stress urinary incontinence (SUI). While non‐degradable synthetic mesh has a low failure rate, it is prone to complications such as infection and erosion, particularly in the urological/gynecological setting when subject to chronic influences of gravity and intermittent, repetitive strain. Biological materials have lower complication rates, although allografts and xenografts have a high risk of failure and the theoretical risk of infection. Autografts are used successfully for the treatment of SUI and are not associated with erosion; however, can lead to morbidity at the donor site. Tissue engineering has thus become the focus of interest in recent years as researchers seek an ideal tissue remodeling material for urogynecological repair. Herein, we review the directions of current and future research in this exciting field. Electrospun poly‐L‐lactic acid (PLA) and porcine small intestine submucosa (SIS) are two promising scaffold material candidates. Adipose‐derived stem cells (ADSCs) appear to be a suitable cell type for scaffold seeding, and cells grown on scaffolds when subjected to repetitive biaxial strain show more appropriate biomechanical properties for clinical implantation. After implantation, an appropriate level of acute inflammation is important to precipitate moderate fibrosis and encourage tissue strength. New research directions include the use of bioactive materials containing compounds that may help facilitate integration of the new tissue. More research with longer follow‐up is needed to ascertain the most successful and safe methods and materials for pelvic organ repair and SUI treatment.

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.

The underactive bladder: detection and diagnosis

The inability to generate a voiding contraction sufficient to allow efficient bladder emptying within a reasonable time frame is a common problem seen in urological practice. Typically, the symptoms that arise are voiding symptoms, such as weak and slow urinary flow. These symptoms can cause considerable bother to patients and impact upon quality of life. The urodynamic finding of inadequate detrusor contraction has been termed detrusor underactivity (DUA). Although a definition is available for this entity, there are no widely accepted diagnostic criteria. Drawing parallels to detrusor overactivity and the overactive bladder, the symptoms arising from DUA have been referred to as the “underactive bladder” (UAB), while attempts to crystallize the definition of UAB are now ongoing. In this article, we review the contemporary literature pertaining to the epidemiology and etiopathogenesis of DUA as well as discuss the definitional aspects that are currently under consideration.

Recent developments in technology for the assessment and management of incontinence

Abstract 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.

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.