Hypospadias repair : an overview of the actual techniques

Hypospadias is one of the most common congenital genital anomalies for which surgery early in life is indicated. The surgical treatment is changing progressively, often by repeating treatment strategies that have been used decades ago. Indeed, historically two-stage procedures were replaced by one-stage procedures and nowadays two-stage procedures gain new interest. The same for reconstructions using the urethral plate, which decades ago were based on the Thiersch Duplay principle. In the 1980s, preputial onlay flaps were most often used and today we see a new interest in the use of the urethral plate. The actual surgical approach to hypospadias is described and technical details are given

Hypoxic changes to the urothelium as a bystander of end-stage bladder disease

Introduction: Urothelial cells harvested from benign diseased bladders have a compromised capacity to propagate or differentiate in vitro, potentially limiting their application in autologous tissue engineering approaches. The causative pathways behind this altered phenotype are unknown. The hypothesis is that hypoxic damage to the urothelium occurs as a bystander to chronic or recurrent episodes of infection and inflammation. Objective: The aim of this study was to assess immunohistochemically detected nuclear hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor in the urothelium when exposed to hypoxia. Study design: Human bladder sections from a total of 29 adult and paediatric patients, representing a variety of different pathologies including neuropathy (n = 15), were analysed. Tissues from adults with bladder outlet obstruction secondary to prostatic disease (n = 1), urothelial carcinoma (n = 1) and tonsil (n = 1) were used as positive tissue controls for immunohistochemistry. Hypoxia-inducible factor 1 alpha–labelled sections were scanned using a Zeiss AxioScan Z1 slide scanner. Analysis of urothelial nuclear HIF-1α labelling was performed using HistoQuest image analysis software (TissueGnostics). Comparison of nuclear HIF-1α labelling between neuropathic and non-neuropathic sections was performed using one-way analysis of variance with the post hoc Tukey honestly significant difference (HSD) test. Patient urodynamic studies performed before tissue sample harvest were evaluated and correlated to the HIF-1α intensity using Spearman's rank correlation. Results: Hypoxia-inducible factor 1 alpha appeared more intense in the urothelial compartment from neuropathic bladder samples (n = 15) than in the control tissues, including non-obstructed samples (n = 9). Image analysis supported this; median nuclear HIF-1α labelling was 29.98 ± 3.10 (standard deviation [SD]) (n = 9) in controls and 74.29 ± 7.55 (SD) in neuropathic samples (n = 15). A statistically significant difference between the control and neuropathic tissue groups was shown (P < 0.05). Of the 15 neuropathic samples, 11 had traceable urodynamic studies. Both initial and maximum detrusor pressures indicated a positive relationship when plotted against HIF-1α labelling. Spearman's rank correlation, with no missing events, confirmed significant correlations between both initial or maximum detrusor pressure and nuclear HIF-1α labelling intensity (median score); P ≤ 0.046 and P ≤ 0.05, respectively. The null hypothesis was accordingly rejected. Conclusions: This study indicates that urothelial nuclear HIF-1α may be a biomarker of hypoxia and a common feature in end-stage bladder disease associated with high-pressure systems

Augmentation of the insufficient tissue bed for surgical repair of hypospadias using acellular matrix grafts : A proof of concept study

Acellular matrices produced by tissue decellularisation are reported to have tissue integrative properties. We examined the potential for incorporating acellular matrix grafts during procedures where there is an inadequate natural tissue bed to support an enduring surgical repair. Hypospadias is a common congenital defect requiring surgery, but associated with long-term complications due to deficiencies in the quality and quantity of the host tissue bed at the repair site. Biomaterials were implanted as single on-lay grafts in a peri-urethral position in male pigs. Two acellular tissue matrices were compared: full-thickness porcine acellular bladder matrix (PABM) and commercially-sourced cross-linked acellular matrix from porcine dermis (Permacol™). Anatomical and immunohistological outcomes were assessed 3 months post-surgery. There were no complications and surgical sites underwent full cosmetic repair. PABM grafts were fully incorporated, whilst Permacol™ grafts remained palpable. Immunohistochemical analysis indicated a non-inflammatory, remodelling-type response to both biomaterials. PABM implants showed extensive stromal cell infiltration and neovascularisation, with a significantly higher density of cells (p < 0.001) than Permacol™, which showed poor cellularisation and partial encapsulation. This study supports the anti-inflammatory and tissue-integrative nature of non-crosslinked acellular matrices and provides proof-of-principle for incorporating acellular matrices during surgical procedures, such as in primary complex hypospadias repair