Niall F. Davis

Xenogenic extracellular matrices as potential biomaterials for interposition grafting in urological surgery.

PURPOSEnThe field of tissue engineering focuses on developing strategies for reconstructing injured, diseased, and congenitally absent tissues and organs. During the last decade urologists have benefited from remodeling and regenerative properties of bioscaffolds derived from xenogenic extracellular matrices. We comprehensively reviewed the current literature on structural and functional characteristics of xenogenic extracellular matrix grafting since it was first described in urological surgery. We also reviewed the clinical limitations, and assessed the potential for safe and effective urological application of extracellular matrix grafting in place of autogenous tissue.nnnMATERIALS AND METHODSnWe performed literature searches for English language publications using the PubMed® and MEDLINE® databases. Keywords included xenogenic, extracellular matrix and genitourinary tract applications. A total of 112 articles were scrutinized, of which 50 were suitable for review based on clinical relevance and importance of content.nnnRESULTSnSince the mid 1990s xenogenic extracellular matrices have been used to successfully treat a number of pathological conditions that affect the upper and lower genitourinary tract. They are typically prepared from porcine organs such as small intestine and bladder. These organs are harvested and subjected to decellularization and sterilization techniques before surgical implantation. Bioinductive growth factors that are retained during the preparation process induce constructive tissue remodeling as the extracellular matrix is simultaneously degraded and excreted. However, recent documented concerns over durability, decreased mechanical strength and residual porcine DNA after preparation techniques have temporarily hampered the potential of extracellular matrices as a reliable replacement for genitourinary tract structures.nnnCONCLUSIONSnExtracellular matrices are a useful alternative for successfully treating a number of urological conditions that affect the genitourinary tract. However, clinical concerns regarding mechanical limitations and biosafety need to be addressed before their long-term role in reconstructive urological surgery can be clearly established.

Evaluation of Endoscopic Laser Excision of Polypropylene Mesh/Sutures Following Anti-Incontinence Procedures

PURPOSEnWe reviewed our experience with and outcome of the largest series to our knowledge of patients who underwent endoscopic laser excision of eroded polypropylene mesh or sutures as a complication of previous anti-incontinence procedures.nnnMATERIALS AND METHODSnA total of 12 female patients underwent endoscopic laser excision of suture/mesh erosions at 1 center during a 10-year period. Primary outcome variables were the requirement of additional endoscopic or open surgery to remove mesh/sutures. Secondary outcome variables were persistence of urinary symptoms, postoperative complications, continence status and requirement of additional anti-incontinence procedures.nnnRESULTSnThe mean interval from previous surgery to erosion was 59 months (range 7 to 144) and the duration of presenting symptoms ranged from 3 to 84 months (mean 19). Ten patients underwent endoscopic excision of the mesh/suture with the holmium:YAG laser and 2 underwent excision with the thulium laser. Mean operative duration was 19 minutes (range 10 to 25) and followup was 65.5 months (range 6 to 134). Postoperatively 6 patients remain asymptomatic and 2 required a rectus fascial sling for recurrent stress urinary incontinence. Four patients underwent a second endoscopic excision due to minor persistence of erosion. Only 1 patient ultimately required open cystotomy to remove the eroded biomaterial. No intraoperative complications were recorded and all patients are currently asymptomatic.nnnCONCLUSIONSnEndoscopic laser excision is an acceptable first line approach for the management of eroded biomaterials due to its high long-term success rate and minimally invasive nature.

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The Pathogenesis of Urinary Tract Infections

Urinary tract infections (UTIs) are among the most common conditions requiring medical treatment with 6-10% of all young females demonstrating bacteriuria (Raz 2001). The incidence of UTIs increases with age and 25-50% of females aged 80 or more have bacteriuria (Abrutyn et al. 1988). UTIs occur as a result of interactions between the uropathogen and host and their pathogenesis involves several processes. Initially the uropathogen attaches to the epithelial surface; it subsequently colonises and disseminates throughout the mucosa causing tissue damage. After the initial colonisation period, pathogens can ascend into the urinary bladder resulting in symptomatic or asymptomatic bacteriuria. Further progression may lead to pyelonephritis and renal impairment. Specific virulence factors residing on the uropathogen’s membrane are responsible for bacterial resistance to the normally effective defence mechanisms of the host. Recently, bacterial adhesins and their associated epithelial binding sites have been identified and natural antiadherence mechanisms are currently under investigation. An understanding of pathogenic and anti-adherence mechanisms may allow physicians to develop appropriate strategies for UTI prevention and adequate management protocols. In the present chapter we discuss current concepts on the pathogenesis of UTIs with particular emphasis on pathogenic bacteria, virulence factors, predisposing factors, natural defences within genitourinary tract and consequences when these defence mechanisms are altered.

Ureteric obstruction due to fungus-ball in a chronically immunosuppressed patient.

Candida albicans is a fungus that can cause opportunistic urinary tract infections in immunocompromised patients. Disseminated fungaemia secondary to Candida albicans is associated with considerable mortality and therefore merits aggressive treatment. Diagnostic investigations for urosepsis and disseminated fungaemaia secondary to Candida albicans include positive urine and blood cultures. Herein, we describe an extremely unusual case of disseminated fungaemia associated with an obstructive fungus-ball in the distal ureter of an immunosuppressed patient. We also describe a novel application of an established endourological technique for managing this clinical scenario and discuss appropriate perioperative management strategies.

Perioperative management of chronic anticoagulation therapy in urological patients: a cross-sectional survey of practice.

BackgroundThere has been a significant increase in the volume of urological patients on daily anticoagulation therapy requiring invasive elective urological procedures.AimsWe sought to assess whether urologists are familiar with appropriate perioperative management strategies in this patient cohort.MethodsUrologists completed a questionnaire on their current management strategy for warfarin during the perioperative period in patients undergoing elective urological surgery. Eleven urological procedures graded as minor, endoscopic and major were assessed in the study. In addition, respondents were also asked whether they administered bridging therapy with heparin when warfarin was discontinued perioperatively.ResultsThe response rate was 52.5% (210/400). Procedure grade did not influence the duration warfarin was discontinued preoperatively with respondents discontinuing the agent 4.71xa0±xa01.52xa0days (range 2–10xa0days) prior to minor procedures, 4.74xa0±xa01.43xa0days (range 2–10xa0days) prior to endoscopic procedures and 4.88xa0±xa01.34xa0days (range 2–10xa0days) prior to major procedures (pxa0>xa00.05). Postoperatively, procedure grade significantly affected the day to recommencement with respondents recommencing warfarin 2.41xa0±xa02.31xa0days (range 1–14xa0days) after minor procedures, 3.07xa0±xa03.52xa0days (range 1–28xa0days) after endoscopic procedures and 4.38xa0±xa03.53xa0days (range 1–14xa0days) after major procedures (pxa0<xa00.0001). In total, 60xa0±xa00.52% of the respondents who discontinued warfarin routinely administered bridging therapy with heparin perioperatively.ConclusionsOur study demonstrates variations in perioperative management practices for patients on chronic anticoagulation therapy undergoing urological procedures. Urologists should familiarise themselves with standardised guidelines if this patient subgroup are to receive optimal perioperative management.

Cell-seeded extracellular matrices for bladder reconstruction: An ex vivo comparative study of their biomechanical properties

Purpose Autogenous ileal tissue remains the gold-standard biomaterial for bladder replacement purposes; however, cell-seeded extracellular matrix (ECM) scaffolds have shown promise. Although the biological advantages of cell-seeded ECMs in urological settings are well documented, there is a paucity of data available on their biomechanical properties. In this study, the biomechanical properties of cell-seeded ECMs are compared with autogenous ileal tissue. Methods Human urothelial cells (UCs) and smooth muscle cells (SMCs) were obtained by bladder biopsy and cultured onto porcine urinary bladder matrix (UBM) scaffolds under dynamic and static growth conditions for 14 days. The biomechanical properties of cell-seeded UBM (n = 12), and porcine ileum (n = 12) were determined with uni-axial tensile testing protocols and compared with stress-strain curves. In addition, their biomechanical properties were compared with porcine bladder tissue (n = 12) and unseeded UBM (n = 12). Results There were significant differences in the biomechanical properties of each biomaterial assessed. Strain to failure occurred at 92 ± 24% for dynamically cultured cell-seeded UBM compared to 42.2 ± 5.20% for ileal tissue (p<0.01). Values for linear stiffness at 30% strain were significantly lower in dynamically cultured cell-seeded UBM compared to ileal tissue (0.36 ± 0.14 MPa versus 0.67 ± 0.32 MPa respectively, p<0.01). Bladder tissue remained the most distensible biomaterial throughout, with linear stiffness measuring 0.066 ± 0.034 MPa at 30% strain. Conclusions Dynamically cultured cell-seeded ECMs are biomechanically superior to ileal tissue for bladder replacement purposes. Additional comparative in vivo studies will be necessary before their role as a reliable alternative is clearly established.

Tissue-Engineered Extracellular Matrices (ECMs) as Adjuvant Scaffolds for Endovascular Aneurysmal Repair (EVAR)

Abdominal aortic aneurysms (AAA) are permanent, irreversible, localised dilatations of they aorta. Usually, they develop as a result of a progressive localised weakness within the vessel wall. They typically occur below the level of the renal arteries and have a high propensity for rupture. In fact, ruptured AAAs account for approximately 8,000 and 15,000 deaths in the United Kingdom (UK) and United States of America (USA) respectively on an annual basis (Sakalihasan et al. 2005, Thompson 2003, Vorp and Vande Geest 2005). Risk factors for their development include male gender, age >65 and a history of smoking. Other associated risk factors are connective tissue disorders that typically have a genetic predisposition, syphilitic infections and cystic medial necrosis. Currently, there are two surgical treatments for AAA; the traditional open repair and a minimally invasive procedure known as endovascular aneurysm repair (EVAR) (Kamineni and Heuser 2004, Parodi et al. 1991, Sakalihasan et al. 2005). The endovascular technique has been widely applied in clinical practice, however important limitations persist (Egelhoff et al. 1999, Kamineni and Heuser 2004, Parodi et al. 1991). Among these limitations are device migration, endoleaks, and thrombotic occlusion. It has been suggested that tissueengineered xenografts may play a role for preventing these complications in EVAR. In the present chapter we discuss limitations of stent-grafts deployed in the EVAR procedure. We place particular emphasis on tissue-engineered extracellular matrices (ECMs) as adjuvant scaffolds for optimisation of the EVAR procedure.

Delayed presentation of a detached resectoscope beak and treatment with thulium laser

Intraoperative detachment of a resectoscope beak is an extremely rare and unusual event. Retrieval of the ceramic beak can be difficult due to the sheaths large size relative to the urethral lumen. Our report describes the retrieval of a calcified ceramic resectoscope beak from the urinary bladder 4 years after transurethral resection of the prostate (TURP). The calcified beak was successfully fragmented into 3 separate pieces with a thulium laser. This method allowed for safe removal of each fragment through the urethra.

Perioperative management of antithrombotic agents in urological surgery

Introduction: There are no published urological guidelines for the management of antithrombotic agents during the perioperative period. Aims: To demonstrate variations in urological perioperative protocols for the antithrombotic agents aspirin, clopidogrel and warfarin. Materials and methods: Consultant urologists from the BAUS registry completed an online questionnaire on perioperative management of antithrombotic agents in urological surgery. Urologists were requested to indicate whether they routinely discontinued aspirin, clopidogrel or warfarin during the perioperative period for 11 different urological procedures. Respondents that discontinued an antithrombotic agent were requested to indicate the number of days the agent was discontinued preoperatively and recommenced postoperatively. Results: Of the 400 urologists surveyed, 210 (52.5%) responded. The percentage of respondents that continued each antithrombotic agent varied widely in each of the 11 procedures assessed (aspirin: range 48–82%; clopidogrel: 1–50%; warfarin: 2–40%). Respondents were most likely to continue an antithrombotic agent prior to diagnostic ureteroscopy (aspirin 82%, clopidogrel 50%, warfarin 40%) and least likely to continue prior to TURP (aspirin 45%, clopidogrel 2%, warfarin 2%). Conclusions: This is the first study addressing urological procedure-specific perioperative management policies for aspirin, clopidogrel and warfarin. Our findings suggest that perioperative management policies for antithrombotic agents are highly variable and appear arbitrary. Standardised guidelines need to be developed to reduce variations in current urological surgical practice.