Tissue-engineered buccal mucosa using silk fibroin matrices for urethral reconstruction in a canine model

Background

To investigate the feasibility of urethral reconstruction using tissue-engineered buccal mucosa (TEBM) with silk fibroin (SF) matrices in a canine model.

Materials and methods

Autologous oral keratinocytes and autologous fibroblasts were isolated, expanded, and seeded onto SF matrices to obtain TEBM. The TEBM was assessed using hematoxylin and eosin staining and scanning electron microscopy. A 5-cm urethral mucosal defect was created in 10 female canines. Urethroplasty was performed using TEBM in five canines in the experimental group and with SF matrices without cells in the five canines in the comparison group. Retrograde urethrography was performed after 6 mo of grafting. The urethral grafts were analyzed grossly and histologically.

Results

The oral keratinocytes and fibroblasts exhibited good biocompatibility with the SF matrices. TEBM could be constructed using SF matrices. The canines implanted with the tissue-engineered mucosa voided without difficulty. The retrograde urethrography revealed no sign of stricture. The histologic staining showed that epithelial cells developed gradually and exhibited stratified epithelial layers at 6 mo. In the comparison group, the canines had difficulty voiding, and the retrograde urethrography showed urethra stricture. The histologic staining showed that one to two layers of epithelial cells developed.

Conclusions

The TEBM using SF matrices could be a potential material for urethra reconstruction.     

Tissue-engineered buccal mucosa urethroplasty-clinical outcomes

INTRODUCTION: Whilst buccal mucosa is the most versatile tissue for urethral replacement, the quest continues for an ideal tissue replacement for the urethra when substantial tissue transfer is needed. Previously we described the development of autologous tissue-engineered buccal mucosa (TEBM). Here we report clinical outcomes of the first human series of its use in substitution urethroplasty. METHODOLOGY: Five patients with urethral stricture secondary to lichen sclerosus (LS) awaiting substantial substitution urethroplasty elected to undergo urethroplasty using TEBM, with full ethics committee support. Buccal mucosa biopsies (0.5 cm) were obtained from each patient. Keratinocytes and fibroblasts were isolated and cultured, seeded onto sterilised donor de-epidermised dermis, and maintained at air-liquid interface for 7-10 d to obtain full-thickness grafts. These grafts were used for urethroplasty in a one-stage (n=2) or a two-stage procedure (n=3). Follow-up was performed at 2 and 6 wk, at 3, 6, 9, and 12 mo, and every 6 mo thereafter. RESULTS: Follow-up ranged from 32 to 37 mo (mean, 33.6). The initial graft take was 100%, as assessed by visual inspection. Subsequently, one patient had complete excision of the grafted urethra and one required partial graft excision, for fibrosis and hyperproliferation of tissue, respectively. Three patients have a patent urethra with the TEBM graft in situ, although all three required some form of instrumentation. CONCLUSIONS: Whilst TEBM may in the future offer a clinically useful autologous urethral replacement tissue, in this group of patients with LS urethral strictures, it was not without complications, namely fibrosis and contraction in two of five patients.     

One-stage repair of long bulbar urethral strictures using augmented Russell dorsal strip anastomosis: outcome of 234 cases

Objectives

Long bulbar urethral strictures (>2 cm) are not amenable to stricture excision and primary anastomosis procedure, which may result in a short urethra and chordee formation. For such strictures many procedures have been advocated including stricturotomy with subsequent graft or flap onlay, augmented anastomosis, and staged procedures, which is a combination of the Russell graft. We present our 10-yr experience with the augmented Russell procedure using a ventral onlay buccal mucosal patch graft for treatment of long bulbar urethral strictures not amenable to excision and primary anastomosis.

Methods

A total of 234 patients diagnosed by urethrograms as having long bulbar urethral strictures (mean, 4.2 cm) were managed by the augmented Russell urethroplasty. The procedure included excision of most of the diseased segment (mean, 2.8 cm) and anastomosis of a dorsal strip leaving an oval ventral defect. Augmentation was done in all patients using a buccal mucosa patch graft (mean, 4.7 cm).

Results

Mean follow-up was 36 mo. Urethrograms were done at 3 wk and 3 and 6 mo postoperatively and if the patients were symptomatic thereafter. Urethrocystoscopy was performed at 12 and 18 mo. A total of 223 patients completed the follow-up protocol; the overall success rate was 93.7% with 14 (6.3%) patients showing stricture recurrence at different intervals postoperatively. Ten patients in the failure group were successfully managed by single visualized internal urethrotomy (VIU), whereas the other four patients were treated by ventral penile pedicled flap. Postoperative dribbling of urine was noticed by 90 patients (40.4%) and temporary perioral numbness in most patients; no major donor site complications were noted in our series.

Conclusion

The augmented Russell technique is beneficial for long bulbar urethral strictures; 93.7% of the patients were stricture free. In the bulbar region, both ventral and dorsal onlays are applicable with nearly equal success rates. The buccal mucosa patch graft offers excellent material for augmentation.     

Transpubic access using pedicle tubularized labial urethroplasty for the treatment of female urethral strictures associated with urethrovaginal fistulas secondary to pelvic fracture

Background

Female urethral injury is rare, and there is no accepted standard approach for the repair of urethral strictures.

Objective

To evaluate the efficacy of transpubic access using pedicle tubularized labial urethroplasty for urethral reconstruction in female patients with urethral obliterative strictures and urethrovaginal fistulas.

Design, setting, and participants

Between January 1996 and December 2006, eight cases of female urethral strictures associated with urethrovaginal fistulas were treated using pedicle labial skin flaps.

Interventions

A flap of approximately 3 × 3.5 × 3 cm of the labia minora or majora with its vascular pedicle was tubularized over an 18–22 Fr fenestrated silicone stent to create a neourethra. This technique was used in five women. Two flaps, approximately 1.5–3.5 cm, were taken from bilateral labia minora or majora and were pieced together to create a neourethra. This technique was used in three patients.

Measurements

We performed voiding cystourethrography and uroflowmetry to assess postoperative results.

Results and limitations

The patients were followed up for 10–118 mo (mean 48.25 mo) after the procedure. There were no postoperative complications. Two patients complained of dysuria, which resolved spontaneously after 2 wk. One patient experienced stress incontinence that resolved after 4 wk. At 3-mo follow-up, one patient complained of difficulty voiding; the urinary peak flow was 13 ml/s, and the patient was treated successfully with urethral dilation. All other patients had normal micturition following catheter removal.

Conclusions

Pedicle labial urethroplasty is a reliable technique for the repair of extensive urethral damage, and a transpubic surgical approach provides wide and excellent exposure for the management of complex obliterative urethral strictures and urethrovaginal fistulas secondary to pelvic fracture.     

Methods to reduce the contraction of tissue-engineered buccal mucosa for use in substitution urethroplasty

Background

We previously described the production and clinical outcomes of tissue-engineered buccal mucosa (TEBM) used to treat recurrent urethral strictures. In this study, two patients developed a recurrent stricture and there was also evidence of graft contraction.

Objective

Assess possible preclinical methods to reduce contraction of TEBM.

Design, setting and participants

Using the model of TEBM in use clinically (ie, oral keratinocytes and fibroblasts cultured on de-epidermised acellular dermal scaffold), three methods of reducing TEBM contraction were investigated in vitro.

Interventions

The techniques assessed were pretreatment of de-epidermised dermis (DED) with glutaraldehyde, culture with β-aminopropionitrile (β-APN; a lysyl oxidase inhibitor), and physical restraint of TEBM grafts during culture.

Measurements

Contraction was assessed using serial digital image analysis. The cytotoxicity of the pharmacologic manipulations was assessed using monolayer cultures of oral mucosa cells.

Results and limitations

Control TEBM lost a mean of 45.4% of its original surface area over 28 d of culture. Treating TEBM with glutaraldehyde, β-APN, or mechanical restraint during culture all significantly inhibited graft contraction. Glutaraldehyde treatment was most effective (only 5.5% loss of area with 0.1% glutaraldehyde), followed by mechanical restraint for at least 7 d (21.4% loss of area), and then β-APN (28.7% loss of area). None of the treatments had any significant effect on cell viability. This in vitro study identifies solutions for graft contracture to explore in the clinic.

Conclusions

Glutaraldehyde pretreatment and restraint of TEBM grafts during culture both reduce graft contraction.     

What is the Best Technique for Urethroplasty?

Context

There is no clear evidence that determines which type of urethroplasty to perform under which particular circumstance.

Objective

To review the options for urethroplasty at different sites in the urethra and for different types of stricture indicating which procedure should be used in which circumstances according to the best available evidence.

Evidence acquisition

Recent publications have been reviewed and supplemented with the authors’ personal experience.

Evidence synthesis

Currently, in the developed world, the most common types of stricture are relatively short and are situated in the bulbar urethra. There is good evidence that these are best treated by excision and end-to-end anastomosis if they are short enough or by patch urethroplasty using a buccal mucosal graft if they are longer.Distal penile urethral strictures are the next most common type of stricture, but the evidence base is weaker, although there is agreement that penile strictures due to lichen sclerosus often require a staged approach to reconstruction, again using buccal mucosal grafts.Urethroplasty for pelvic fracture urethral injury is an altogether different type of technique for an altogether different type of pathology. There is good evidence that this is best treated by bulbo-prostatic anastomotic urethroplasty.Other types of strictures and salvage surgery have no good evidence base and are specialised areas where experience and judgement are necessary.

Conclusions

The evidence base for urethral surgery has been developed for the more common types of urethral strictures in the last 20 yr, but it is still as much an art as it is a science.     

Evaluation of stretched electrospun silk fibroin matrices seeded with urothelial cells for urethra reconstruction

Background

We investigated the feasibility of urethral reconstruction using stretched electrospun silk fibroin matrices.

Materials and methods

A novel electrospun silk fibroin matrix was prepared. The structure of the material was assessed by scanning electron microscopy and a porosity test. Canine urothelial cells were isolated, expanded, and seeded onto the material for 1 wk to obtain a tissue-engineered graft. The tissue-engineered graft was assessed using hematoxylin and eosin staining and scanning electron microscopy. A dorsal urethral mucosal defect was created in nine female beagle dogs. In the experimental group, tissue-engineered mucosa was used to repair urethra mucosa defects in six dogs. No substitute was used in the three dogs of the control group. Retrograde urethrography was performed at 1, 2, and 6 mo after grafting. The urethral grafts were analyzed grossly and histologically.

Results

Scanning electron microscope and a porosity test revealed that the material had a three-dimensional porous structure. Urothelial cells grew on the material and showed good biocompatibility with the stretched silk fibroin matrices. Canines implanted with tissue-engineered mucosa voided without difficulty. Retrograde urethrography revealed no signs of stricture. Histologic staining showed gradual epithelial cell development and stratified epithelial layers at 1, 2, and 6 mo. The canines in the control group showed difficulty in voiding. Retrograde urethrography showed urethra stricture. Histologic staining showed that no or only one layer of epithelial cells developed. A severe inflammatory reaction was also observed in the control group.

Conclusions

Stretched electrospun silk fibroin matrices have good biocompatibility with urothelial cells, which could prove to be a potential material for use in urethra reconstruction.     

A systematic review of graft augmentation urethroplasty techniques for the treatment of anterior urethral strictures

Context

Reconstructive surgeons who perform urethroplasty have a variety of techniques in their armamentarium that may be used according to factors such as aetiology, stricture position, and length. No one technique is recommended.

Objective

Our aim was to assess the reported outcomes of the various techniques for graft augmentation urethroplasty according to site of surgery.

Evidence acquisition

We performed an updated systematic review of the Medline literature from 1985 to date and classified the data according to the site of surgery and technique used. Data are also presented on the type of graft used and the follow-up methodology used by each centre.

Evidence synthesis

More than 2000 anterior urethroplasty procedures have been described in the literature. When considering the bulbar urethra there is no significant difference between the average success rates of the dorsal and the ventral onlay procedures, 88.4% and 88.8% at 42.2 and 34.4 mo in 934 and 563 patients, respectively. The lateral onlay technique has only been described in six patients and has a reported success rate of 83% at 77 mo. The Asopa and Palminteri techniques have been described in 89 and 53 patients with a success rate of 86.7% and 90.1% at 28.9 and 21.9 mo, respectively. When considering penile strictures, the success rate of the two-stage penile technique is significantly better than the one-stage penile technique, 90.5% versus 75.7% as calculated for 129 and 432 patients, respectively, although the follow-up of one-stage procedures was longer at 32.8 mo compared with 22.2 mo.

Conclusions

There is no evidence in the literature of a difference between one-stage techniques for urethroplasty of the bulbar urethra. The two-stage technique has better reported outcomes than a one-stage approach for penile urethroplasty but has a shorter follow-up.     

A Prospective Patient-centred Evaluation of Urethroplasty for Anterior Urethral Stricture Using a Validated Patient-reported Outcome Measure

Background

Studies of interventions for urethral stricture have inferred patient benefit from clinician-driven outcomes or questionnaires lacking scientifically robust evidence of their measurement properties for men with this disease.

Objective

To evaluate urethral reconstruction from the patients’ perspective using a validated patient-reported outcome measure (PROM).

Design, setting, and participants

Forty-six men with anterior urethral stricture at four UK urology centres completed the PROM before (baseline) and 2 yr after urethroplasty.

Intervention

A psychometrically robust PROM for men with urethral stricture disease.

Outcome measurements and statistical analysis

Lower urinary tract symptoms (LUTS), health status, and treatment satisfaction were measured, and paired t and Wilcoxon matched-pairs tests were used for comparative analysis.

Results and limitations

Thirty-eight men underwent urethroplasty for bulbar stricture and eight for penile stricture. The median (range) follow-up was 25 (20–30) mo. Total LUTS scores (0 = least symptomatic, 24 = most symptomatic) improved from a median of 12 at baseline to 4 at 2 yr (mean [95% confidence interval (CI)] of differences 6.6 [4.2–9.1], p < 0.0001). A total of 33 men (72%) felt their urinary symptoms interfered less with their overall quality of life, 8 (17%) reported no change, and 5 (11%) were worse 2 yr after urethroplasty. Overall, 40 men (87%) remained “satisfied” or “very satisfied” with the outcome of their operation. Health status visual analogue scale scores (100 = best imaginable health, 0 = worst) 2 yr after urethroplasty improved from a mean of 69 at baseline to 79 (mean [95% CI] of differences 10 [2–18], p = 0.018). Health state index scores (1 = full health, 0 = dead) improved from 0.79 at baseline to 0.89 at 2 yr (mean [95% CI] of differences 0.10 [0.02–0.18), p = 0.012]).

Conclusions

This is the first study to prospectively evaluate urethral reconstruction using a validated PROM. Men reported continued relief from symptoms with related improvements in overall health status 2 yr after urethroplasty. These data can be used as a provisional reference point against which urethral surgeons can benchmark their performance.     

DORSAL ONLAY GRAFT URETHROPLASTY USING PENILE SKIN OR BUCCAL MUCOSA IN ADULT BULBOURETHRAL STRICTURES

Purpose

Preputial skin graft is used routinely for urethral reconstruction in patients with stricture disease. Alternative donor sites include extrapenile skin, bladder mucosa and buccal mucosa. Recently buccal mucosa graft has been suggested when local epithelial tissue is not available. We describe our experience with 37 patients undergoing 1-stage correction of bulbar urethral stricture using a penile skin (31) or buccal mucosa (6) graft.

Materials and Methods

In 37 patients with bulbar urethral strictures a nontubularized dorsal onlay graft was used for urethral reconstruction. A preputial skin graft was used in 31 patients and a buccal mucosa graft in 6 with a paucity of local skin. Buccal mucosa graft length ranged from 2.5 to 5 cm. (average 4) and preputial skin graft was 2.5 to 12 cm. long (average 4.7). A dorsal approach to the urethral lumen was used in all patients who underwent onlay graft urethroplasty.

Results

Mean followup was 21.5 months for all 37 patients, 23 months for 31 treated with preputial skin graft and 13.5 months for 6 treated with buccal mucosa graft. The clinical outcomes were considered a failure anytime postoperative instrumentation was needed, including dilatation. In the series 34 cases (92%) were classified as a success and 3 (8%) as failure.

Conclusions

Onlay graft urethroplasty provided excellent results in 92% of adults with bulbourethral stricture. The dorsal approach to the urethra allowed the use of foreskin or buccal mucosa graft for reconstruction of the adequate urethral lumen.     

Cell-Seeded Tubularized Scaffolds for Reconstruction of Long Urethral Defects: A Preclinical Study

Background

The treatment options for patients requiring repair of a long segment of the urethra are limited by the availability of autologous tissues. We previously reported that acellular collagen-based tubularized constructs seeded with cells are able to repair small urethral defects in a rabbit model.

Objective

We explored the feasibility of engineering clinically relevant long urethras for surgical reconstruction in a canine preclinical model.

Design, setting, and participants

Autologous bladder epithelial and smooth muscle cells from 15 male dogs were grown and seeded onto preconfigured collagen-based tubular matrices (6 cm in length). The perineal urethral segment was removed in 21 male dogs. Urethroplasties were performed with tubularized collagen scaffolds seeded with cells in 15 animals. Tubularized constructs without cells were implanted in six animals. Serial urethrography and three-dimensional computed tomography (CT) scans were performed pre- and postoperatively at 1, 3, 6, and 12 mo. The animals were euthanized at their predetermined time points (three animals at 1 mo, and four at 3, 6, and 12 mo) for analyses.

Outcome measurements and statistical analysis

Statistical analysis of CT imaging and histology was not needed.

Results and limitations

CT urethrograms showed wide-caliber urethras without strictures in animals implanted with cell-seeded matrices. The urethral segments replaced with acellular scaffolds collapsed. Gross examination of the urethral implants seeded with cells showed normal-appearing tissue without evidence of fibrosis. Histologically, an epithelial cell layer surrounded by muscle fiber bundles was observed on the cell-seeded constructs, and cellular organization increased over time. The epithelial and smooth muscle phenotypes were confirmed using antibodies to pancytokeratins AE1/AE3 and smooth muscle–specific desmin. Formation of an epithelial cell layer occurred in the unseeded constructs, but few muscle fibers formed.

Conclusions

Cell-seeded tubularized collagen scaffolds can be used to repair long urethral defects, whereas scaffolds without cells lead to poor tissue development and strictures. This study demonstrates that long tissue-engineered tubularized urethral segments may be used for urethroplasty in patients.     

Morbidity of Oral Mucosa Graft Harvesting from a Single Cheek

Background

The oral mucosa (OM) is a popular substitute for urethroplasty.

Objective

The aim of this study was to investigate oral morbidity and patient satisfaction in a homogeneous group of patients who underwent OM harvesting.

Design, setting, and participants

This study is a prospective analysis of 350 patients who underwent OM harvesting from a single cheek.

Intervention

The graft was harvested in an ovoid shape with closure of the wound. Standard graft size was 4 cm in length and 2.5 cm in width.

Measurements

Self-administered, nonvalidated semiquantitative (0, absence of complications or symptoms; 3, the worst complication or symptom) questionnaire consisting of six questions was used to investigate early complications, with 13 questions designed to investigate late complications and patient satisfaction.

Results and limitations

Early complications included bleeding, which occurred in 15 patients (4.3%); two patients required immediate surgical revision of the harvesting site. The majority of patients (85.2%) showed no pain, and only 3.7% of patients required use of anti-inflammatory drugs. The majority of patients (65.8%) showed slight or moderate swelling. With respect to late complications, most of the patients (73.4%) reported oral numbness for 1 wk, 22.9% for 1 mo, and 3.77% for 3 mo. Numbness resulting from scarring was absent or slight in most of patients. Changes in oral sensitivity occurred in 2.3% of patients. No difficulties opening the mouth or smiling was found in 98.3% and 99.7% of patients, respectively. Slight or moderate dry mouth was found in 97.1% of patients. In response to the question, “Would you undergo oral mucosa graft harvesting using this technique again,” 343 patients (98%) replied “yes,” and 7 patients (2%) replied “no.”

Conclusions

The harvesting of an OM ovoid graft from a cheek with closure of the wound is a safe procedure with a high patient satisfaction rate.     

Periurethral Suspension Stitch During Robot-Assisted Laparoscopic Radical Prostatectomy: Description of the Technique and Continence Outcomes

Background

Several studies have shown that robot-assisted laparoscopic radical prostatectomy (RALP) is feasible, with favorable complication rates and short hospital times. However, the early recovery of urinary continence remains a challenge to be overcome.

Objective

We describe our technique of periurethral retropubic suspension stitch during RALP and report its impact on early recovery of urinary continence.

Design, setting, and participants

We analyze prospectively 331 consecutive patients who underwent RALP, 94 without the placement of suspension stitch (group 1) and 237 with the application of the suspension stitch (group 2).

Surgical procedure

The only difference between the groups was the placement of the puboperiurethral stitch after the ligation of the dorsal venous complex (DVC). The periurethral retropubic stitch was placed using a 12-in monofilament polyglytone suture on a CT-1 needle. The stitch was passed from right to left between the urethra and DVC, and then through the periostium on the pubic bone. The stitch was passed again through the DVC, and then through the pubic bone in a figure eight, and then tied.

Measurements

Continence rates were assessed with a self-administered validated questionnaire (Expanded Prostate Cancer Index Composite [EPIC]) at 1, 3, 6, and 12 mo after the procedure. Continence was defined as the use of no absorbent pads or no leakage of urine.

Results and limitations

In group 1, the continence rate at 1, 3, 6, and 12 mo postoperatively was 33%, 83%, 94.7%, and 95.7%, respectively; in group 2, the continence rate was 40%, 92.8%, 97.9%, and 97.9%, respectively. The suspension technique resulted in significantly greater continence rates at 3 mo after RALP (p = 0.013). The median/mean interval to recovery of continence was also statistically significantly shorter in the suspension group (median: 6 wk; mean: 7.338 wk; 95% confidence interval [CI]: 6.387–8.288) compared to the nonsuspension group (median: 7 wk; mean: 9.585 wk; 95% CI: 7.558–11.612; log rank test, p = 0.02).

Conclusions

The suspension stitch during RALP resulted in a statistically significantly shorter interval to recovery of continence and higher continence rates at 3 mo after the procedure.     

Female gender and carcinoma in situ in the prostatic urethra are prognostic factors for recurrence, progression, and disease-specific mortality in T1G3 bladder cancer patients treated with bacillus Calmette-Guérin

Background

Controversy exists over the most important prognostic factors in T1 high-grade non–muscle-invasive bladder cancer (NMIBC) patients treated with bacillus Calmette-Guérin (BCG).

Objective

Evaluate prognostic factors for recurrence, progression, and disease-specific mortality after adjuvant intravesical BCG immunotherapy in patients with T1G3 NMIBC and long-term follow-up.

Design, setting, and participants

A single-institution retrospective analysis of 146 patients with primary stage T1G3 NMIBC.

Intervention

All patients were treated with complete transurethral resection (TUR) plus multiple bladder biopsies that included the prostatic urethra. No second TUR was done. Patients underwent an induction course of intravesical BCG (Connaught strain, 81 mg) without maintenance therapy.

Measurements

The variables analysed for time to recurrence, progression, and death due to bladder cancer (BCa) were gender, age, tumour multiplicity, diameter, aspect, substaging, concomitant carcinoma in situ (CIS), and CIS in the prostatic urethra. Cox regression models were used to assess the univariate and multivariate prognostic importance of these factors and estimate hazard ratios (HRs). Time-to-event distributions were estimated using cumulative incidence functions.

Results and limitations

The median follow-up was 8.7 yr. Sixty-five patients (44.5%) had recurrence, 25 patients (17.1%) had progression, and 18 patients (12.3%) died because of BCa. Female gender and presence of CIS in the prostatic urethra were associated with an increased risk of recurrence (p = 0.0003, HR: 2.53), progression (p = 0.001, HR: 3.59), and death due to BCa (p = 0.004, HR: 3.53).

Conclusions

In primary T1G3 bladder tumours treated with induction BCG, female gender or having CIS in the prostatic urethra were the only prognostic factors for time to recurrence, progression, and disease-related mortality. It is very important to perform a biopsy of the prostatic urethra in patients with primary high-grade NMIBC as a first step to obtain this prognostic information.     

Adjuvant High-Dose Intensity-Modulated Radiotherapy after Radical Prostatectomy for Prostate Cancer: Clinical Results in 104 Patients

Background

Approximately 25% of patients treated with adjuvant radiotherapy (RT) will develop a biochemical failure within 5 yr after RT when doses of 60–64 Gray (Gy) are used.

Objective

To report on the safety and biochemical outcome of adjuvant intensity-modulated RT (IMRT) with doses >70 Gy.

Design, setting, and participants

Between 1999 and 2008, 104 patients underwent radical prostatectomy (RP) followed by adjuvant IMRT with or without androgen deprivation (AD) with a median follow-up of 36 mo. Indications for adjuvant IMRT were capsule perforation, seminal vesicle invasion (SVI) and/or positive surgical margins at prostatectomy specimen. All patients were irradiated at a single tertiary academic centre. AD was initiated on the basis of SVI, a preprostatectomy prostate-specific antigen level >20 ng/ml, Gleason score ≥4 + 3 (n = 36), or personal preference of the referring urologist (n = 32).

Intervention

A median dose of 74 Gy was prescribed to the planning target volume using IMRT in all patients. AD consisted out of a luteinising hormone-releasing hormone analogue for 6 mo.

Measurements

We report on acute and late toxicity, biochemical relapse–free survival (bRFS), and clinical progression. The Kaplan-Meier method was used to estimate bRFS. Univariate analysis was used to examine the influence of patient- and treatment-related factors on bRFS.

Results and limitations

With respect to acute toxicity, no patients developed grade 3 gastrointestinal (GI) toxicity, and eight patients developed grade 3 genitourinary (GU) toxicity (8%). With respect to late toxicity, no patients developed grade 3 GI toxicity, and four patients (4%) developed grade 3 GU toxicity. A urethral stricture was observed in six patients (6%). The 3- and 5-yr actuarial bRFS was 93%. On univariate analysis, bRFS rates were worse when SVI (p < 0.02), Gleason score ≥4 + 3 (p < 0.02), or negative surgical margins (p < 0.02) were present. AD did not influence bRFS. Six patients had a clinical relapse.

Conclusions

Adjuvant high-dose IMRT after prostatectomy is safe and bRFS is excellent.     

Prevention of recurrent urinary tract infections by intravesical administration of hyaluronic acid and chondroitin sulphate: a placebo-controlled randomised trial

Background

Urinary tract infection (UTI) is a prevalent condition in women during their lifetime with a high rate of recurrence within 3–6 mo.

Objectives

Our aim was to investigate the efficacy and tolerability of the intravesical administration of combined hyaluronic acid (HA) and chondroitin sulphate (CS) in female patients with a history of recurrent UTI.

Design, setting, and participants

We conducted a prospective, randomised, double-blind, placebo-controlled study comparing the intravesical instillation of HA-CS with placebo in women with recurrent UTI.

Intervention

Participants were randomised to receive 50 ml of sterile sodium HA 1.6% and CS 2.0% solution (IALURIL^®) weekly for 4 wk and then monthly for 5 mo.

Measurements

The primary end point of the study was defined as the mean number of UTI per patient per year. Participants were evaluated addressing UTI status/urinary symptoms and with a general health-related quality-of-life (QoL) questionnaire at baseline and after 3, 6, 9, and 12 mo.

Results and limitations

In the intention-to-treat analysis, 57 women were randomly allocated to HA-CS (n = 28) or placebo (n = 29). The UTI rate per patient per year at the end of the study (12 mo) (mean ± SD: −86.6% ± 47.6 vs −9.6% ± 24.6; mean difference: 77%; 95% confidence interval, 72.3–80.8; p = 0.0002) and the mean time to UTI recurrence (52.7 ± 33.4 vs 185.2 ± 78.7 d; p < 0.001) were significantly reduced after treatment with HA-CS compared with placebo. Overall urinary symptoms and QoL measured by questionnaires significantly improved compared with placebo (Pelvic Pain and Urgency/Frequency questionnaire symptom score: 14.53 ± 4.32 vs 9.88 ± 6.77; p = 0.004; SF-36 QoL score: 78.6 ± 6.44 vs 53.1 ± 4.72; p < 0.001). No serious adverse event was reported.

Conclusions

Compared with placebo, HA-CS intravesical instillations significantly reduced UTI rate without severe side effects while improving symptoms and QoL over a 12-mo period in patients with recurrent UTI.

Trial registration

ISRCTN 76354426.     

Improved skin wound epithelialization by topical delivery of soluble factors from fibroblast aggregates

Introduction

Timely coverage of an excised burn wound with a split-thickness skin graft, and efficient epithelialization at the donor site wound are key components in the treatment of burn patients. Prompt healing is dependent on paracrine support from underlying dermal connective tissue fibroblasts.

Study aim

Using the skin graft donor site in pig as a model for epithelialization, our aim was to evaluate if dermal signals, derived from cultured dermal fibroblast aggregates (Finectra), can promote epidermal regeneration.

Materials and methods

Partial-thickness skin wounds were made with a dermatome on the backs of three domestic pigs. After randomization, topical treatment was initiated by application of Finectra (n = 6) or factors from standard fibroblast monolayer cultures (n = 6) trapped in a slow-clotting fibrin matrix. Saline was applied to contralateral wounds to serve as corresponding untreated controls (n = 12). After 3 days, full-thickness skin samples representing the whole wound area were obtained. Histological sections of these samples were analyzed for epithelialization, cell migration from lateral wound edges and hair follicles, as well as for formation of granulation tissue.

Results

In response to topical delivery of Finectra, a significant acceleration of epithelialization (p < 0.001) across the wound surface as well as from the wound edges was evident. Marked increase in thickness of granulation tissue (p < 0.001) was noted in wounds treated with Finectra. Epihelialization originated from adnexal structures in which epithelial islets showed positive staining for cytokeratin-14 and PCNA.

Conclusion

These data show that the fibroblast aggregate-derived paracrine mediators, Finectra, stimulate epidermal regeneration in vivo.     

Robotic partial nephrectomy versus laparoscopic cryoablation for the small renal mass

Background

Open partial nephrectomy (OPN) remains the gold standard for treatment of small renal masses (SRMs). Laparoscopic cryoablation (LCA) has provided encouraging outcomes. Robotic partial nephrectomy (RPN) represents a new promising option but is still under evaluation.

Objective

Compare the outcomes of RPN and LCA in the treatment of patients with SRMs.

Design, setting, and participants

We retrospectively analyzed the medical charts of patients with SRMs (≤4 cm) who underwent minimally invasive nephron-sparing surgery (RPN or LCA) in our institution from January 1998 to December 2010.

Intervention

RPN and LCA.

Measurements

Perioperative complications and functional and oncologic outcomes were analyzed.

Results and limitations

A total of 446 SRMs were identified in 436 patients (RPN, n = 210; LCA, n = 226). Patients undergoing RPN were younger (p < 0.0001), had a lower American Society of Anesthesiologists score (p < 0.001), and higher baseline preoperative estimated glomerular filtration rate (eGFR) (p < 0.0001). Mean tumor size was smaller in the LCA group (2.2 vs 2.4 cm; p = 0.004). RPN was associated with longer operative time (180 vs 165 min; p = 0.01), increased estimated blood loss (200 vs 75 ml; p < 0.0001), longer hospital stay (72 vs 48 h; p < 0.0001), and higher morbidity rate (20% vs 12%, p = 0.015). Mean follow-ups for RPN and LCA were 4.8 mo and 44.5 mo, respectively (p < 0.0001). Local recurrence rates for RPN and LCA were 0% and 11%, respectively (p < 0.0001). Mean eGFR decrease after RPN and LCA was insignificant at 1 mo, at 6 mo after surgery, and during last follow-up. Limitations include retrospective study design, length of follow-up, and selection bias.

Conclusions

Both techniques remain viable treatment options in the management of SRMs. A higher incidence of perioperative complications was found in patients undergoing RPN. However, the technique was not predictive of the occurrence of postoperative complications. Early oncologic outcomes are promising for RPN, which also seems to be associated with better preservation of renal function. Long-term follow-up and well-designed prospective comparative studies are awaited to corroborate these findings.     

A Systematic Review of Surgical Techniques Used in the Treatment of Female Urethral Stricture

Context

Female urethral stricture (FUS) is a rare and challenging clinical entity. Several new surgical techniques have been described for the treatment of FUS, although with the limited number of reports, there is no consensus on best management.

Objective

We evaluated the evidence for surgical interventions reported for treating FUS.

Evidence acquisition

We performed a systematic review of the PubMed and Scopus databases, classifying the results by surgical technique and type of graft in the case of graft augmentation urethroplasty.

Evidence synthesis

A total of 221 patients have been reported on with outcome measures after intervention for FUS. The mean age of women was 51.8 yr of age (range: 22–91). All studies were retrospective case series. There was no consistent definition of FUS nor unified diagnostic criteria. Most studies used a combination of diagnostic tests. Where aetiology was defined, idiopathic and iatrogenic stricture were the two most common causes. Ninety-eight patients underwent prior intervention for FUS, mostly urethral dilatation or urethrotomy. Success was defined as the lack of need for further intervention. Urethral dilatation, assessed in 107 patients, had a mean success rate of 47% at a mean follow-up of 43 mo. Fifty-eight patients had vaginal or labial flap augmentation, with a mean success rate of 91% at 32.1 mo of mean follow-up. Vaginal or labial graft augmentation had a mean success rate of 80% in 25 patients at a mean follow-up of 22 mo. Oral mucosal augmentation, performed in 32 patients, had a mean success rate of 94% at 15 mo of mean follow-up. No instances of de novo stress incontinence were reported.

Conclusion

The techniques of urethroplasty all have a higher mean success rate (80–94%) than urethral dilatation (<50%), although with shorter mean follow-up. Urethroplasty in experienced hands appears to be a feasible option in women who have failed urethral dilatation, although there is a lack of high-level evidence to recommend one technique over another.