Comparative study between porcine small intestinal submucosa and buccal mucosa in a partial urethra substitution in rabbits.

PURPOSE: Several urethral conditions may require tissue substitution. One collagen-base biomaterial that recently emerged as an option is small intestinal submucosa (SIS). The aim of this study was to compare the results of SIS and buccal mucosa for urethral substitution in rabbits. MATERIALS AND METHODS: Thirty-six North Folk male rabbits were randomized into three groups. In all animals, a 10 × 5 mm urethral segment was excised, and the urethral defect was repaired using a one-layer SIS patch (group I [GI]); four-layer SIS (group II [GII]); or buccal mucosa (group III [GIII]). Urethrography was performed preoperatively and after 12 weeks. After sacrifice, graft retraction was objectively measured using Scion Image(®) computer analysis and by calculation of ellipse area. The grade of fibrosis, inflammatory reaction, vascular/epithelial regeneration, and collagen III/I ratio were analyzed by hematoxylin/eosin and Picrosirius red staining. RESULTS: Urethrography confirmed a wide urethral caliber without any signs of strictures after surgery. Urethral fistulae was diagnosed in 8.3% of cases (1 animal each group). Average graft shrinkage was 55.2% in GI; 44.2% in GII; and 57.2% in GIII (p<0.05). The intensity of chronic inflammation, fibrosis, epithelium regeneration, and neovascularization was similar in all groups (p>0.05). Collagen III/I ratio was higher in GII (GI: 119.6; GII: 257.2 and GIII: 115.0); p<0.01. CONCLUSIONS: The four-layer SIS is more advantageous than the one-layer SIS and buccal mucosa for urethral substitution in rabbits.

[Reconstructive urethroplasty using porcine acellular matrix (SIS): evolution of the grafting technique and results of 10-year experience]. / Uretroplastica ricostruttiva con matrice acellularesuina (SIS): evoluzione della tecnica di impiantoe risultati di 10 anni di esperienza.

INTRODUCTION: Long tract urethral reconstruction still has no other resolution than two-stage techniques or graft and flap procedures, that are neither simple nor trouble-free. Tissue engineering simplifies this surgery using porcine acellular matrix, obtained from small intestine submucosa (SIS): thin but strong, ready for grafting, it is not immunogenic, being deprived of cells. It is a biological bridge for reconstruction, promoting the regeneration of surrounding tissue. We report our experience using SIS for urethroplasty. MATERIALS AND METHODS: After coronal or perineal-scrotal incision and penile degloving, the urethra is rotated of 180° and opened through the entire restricted tract. The graft is sutured dorsally and reinforced by the contact with the cavernous bodies to prevent pouching. From 1999 to 2005 we performed this grafting procedure in 36 men and 4 women. Afterwards, 16 more surgeries performed were with direct ventral graft procedure, without urethra isolation and rotation, with worthy simplification. RESULTS: A 10-year follow-up shows satisfactory urodynamic and subjective outcomes for both procedures, assessed by voiding urethrography, uroflowmetry, International Prostate Symptom Score, and Quality of Life perception. At urethroscopy the graft appears completely homogeneous to the native tissue, as confirmed by the histological examination. The ventral direct graft represents the more consistent innovation: we did not observe pouching and the results remained effective. For penile urethra, in a few patients, periodic dilatations were necessary. CONCLUSIONS: SIS can be considered as an alternative to more difficult grafting procedures, which are probably no more indispensable in urethral enlargement, even for critical strictures

Anterior vaginal wall prolapse: a randomized controlled trial of SIS graft versus traditional colporrhaphy.

INTRODUCTION AND HYPOTHESIS: This study seeks to compare the small intestine submucosa (SIS) graft with traditional colporrhaphy (TC) for surgical treatment of anterior vaginal prolapse. METHODS: Subjects were randomly assigned to SIS (n = 29) or to TC (n = 27) preoperatively and outcomes analyzed at 12 months postoperatively. The primary outcome was the absence of POP-Q stage >or= II prolapse, and secondary outcome was improvement in quality of life. Data were compared with independent samples or paired Student's t test. RESULTS: SIS group had 86.2% anatomic cure compared to 59.3% in TC (p = 0.03). SIS improved point Ba measurement significantly (-1.93 cm versus -1.37 cm, p = 0.02). Both operations significantly improved quality of life, although there were no differences between the groups. We observed a greater number of complications in the SIS group, with no infections or erosion. CONCLUSIONS: SIS repair improved point Ba significantly. However, there were no differences observed in quality of life between the techniques.

Non-traditional management of the neurogenic bladder: tissue engineering and neuromodulation.

Patients with spina bifida and a neurogenic bladder have traditionally been managed with clean intermittent catheterization and pharmacotherapy in order to treat abnormal bladder wall dynamics, protect the upper urinary tract from damage, and achieve urinary continence. However, some patients will fail this therapy and require surgical reconstruction in the form of bladder augmentation surgery using reconfigured intestine or stomach to increase the bladder capacity while reducing the internal storage pressure. Despite functional success of bladder augmentation in achieving a low pressure reservoir, there are several associated complications of this operation and patients do not have the ability to volitionally void. For these reasons, alternative treatments have been sought. Two exciting alternative approaches that are currently being investigated are tissue engineering and neuromodulation. Tissue engineering aims to create new bladder tissue for replacement purposes with both "seeded" and "unseeded" technology. Advances in the fields of nanotechnology and stem cell biology have further enhanced these tissue engineering technologies. Neuromodulation therapies directly address the root of the problem in patients with spina bifida and a neurogenic bladder, namely the abnormal relationship between the nerves and the bladder wall. These therapies include transurethral bladder electrostimulation, sacral neuromodulation, and neurosurgical techniques such as selective sacral rhizotomy and artificial somatic-autonomic reflex pathway construction. This review will discuss both tissue engineering techniques and neuromodulation therapies in more detail including rationale, experimental data, current status of clinical application, and future direction.

Effects of L-arginine on serum nitric oxide, nitric oxide synthase and mucosal Na+-K+-ATPase and nitric oxide synthase activity in segmental small-bowel autotransplantation model.

AIM: To explore a simple method to create intestinal autotransplantation in rats and growing pigs and to investigate the effect of L-arginine supplementation on serum nitric oxide (NO), nitric oxide synthase (NOS) and intestinal mucosal NOS and Na+-K+-ATPase activity during cold ischemia-reperfusion (IR) in growing pigs. METHODS: In adult Wistar rat models of small bowel autotransplantation, a fine tube was inserted into mesenteric artery via the abdominal aorta. The superior mesenteric artery and vein were occluded. Isolated terminal ileum segment was irrigated with Ringer's solution at 4 degrees and preserved in the same solution at 0-4 degrees for 60 min. Then, the tube was removed and reperfusion was established. In growing pig models, a terminal ileum segment, 50 cm in length, was isolated and its mesenteric artery was irrigated via a needle with lactated Ringer's solution at 4 degrees. The method and period of cold preservation and reperfusion were described above. Ten white outbred pigs were randomly divided into control group and experimental group. L-arginine (150 mg/kg) was continuously infused for 15 min before reperfusion and for 30 min after reperfusion in the experimental group. One, 24, 48, and 72 h after reperfusion, peripheral vein blood was respectively collected for NO and NOS determination. At the same time point, intestinal mucosae were also obtained for NOS and Na+-K+-ATPase activity measurement. RESULTS: In adult rat models, 16 of 20 rats sustained the procedure, three died of hemorrhage shock and one of deep anesthesia. In growing pig models, the viability of small bowel graft remained for 72 h after cold IR in eight of 10 pigs. In experimental group, serum NO level at 1 and 24 h after reperfusion increased significantly when compared with control group at the same time point (152.2+/-61.4 micromol/L vs 60.8+/-31.6 micromol/L, t=2.802, P=0.02<0.05; 82.2+/-24.0 micromol/L vs 54.0+/-24.3 micromol/L, t=2.490, P=0.04<0.05). Serum NO level increased significantly at 1 h post-reperfusion when compared with the same group before cold IR, 24 and 48 h post-reperfusion (152.2+/-61.4 micromol/L vs 75.6+/-16.2 micromol/L, t=2.820, P=0.02<0.05, 82.2+/-24.0 micromol/L, t=2.760, P=0.03<0.05, 74.2+/-21.9 micromol/L, t=2.822, P=0.02<0.05). Serum NOS activity at each time point had no significant difference between two groups. In experimental group, intestinal mucosal NOS activity at 1 h post-reperfusion reduced significantly when compared with pre-cold IR (0.79+/-0.04 U/mg vs 0.46+/-0.12 U/mg, t=3.460, P=0.009<0.01). Mucosal NOS activity at 24, 48, and 72 h post-reperfusion also reduced significantly when compared with pre-cold IR (0.79+/-0.04 U/mg vs 0.57+/-0.14 U/mg, t=2.380, P=0.04<0.05, 0.61+/-0.11 U/mg, t=2.309, P=0.04<0.05, 0.63+/-0.12 U/mg, t=2.307, P=0.04<0.05). In control group, mucosal NOS activity at 1 and 24 h post-reperfusion was significantly lower than that in pre-cold IR (0.72+/-0.12 U/mg vs 0.60+/-0.07 U/mg, t=2.320, P=0.04<0.05, 0.58+/-0.18 U/mg, t=2.310, P=0.04<0.05). When compared to the normal value, Na+-K+-ATPase activity increased significantly at 48 and 72 h post-reperfusion in experimental group (2.48+/-0.59 micromol/mg vs 3.89+/-1.43 micromol/mg, t=3.202, P=0.04<0.05, 3.96+/-0.86 micromol/mg, t=3.401, P=0.009<0.01) and control group (2.48+/-0.59 micromol/mg vs 3.58+/-0.76 micromol/mg, t=2.489, P=0.04<0.05, 3.67+/-0.81 micromol/mg, t=2.542, P=0.03<0.05). CONCLUSION: This novel technique for intestinal autotransplantation provides a potentially consistent and practical model for experimental studies of graft cold preservation. L-arginine supplementation during cold IR may act as a useful adjunct to preserve the grafted intestine.

Glutamine metabolism of intestine grafts: influence of mucosal injury by prolonged preservation and transplantation.

The demand for glutamine increased only in the preserved intestine in the early postoperative period (3 days after transplantation). Glutamine demand of the preserved grafts returned to control and immediate levels 7 and 14 days after transplantation. Three days after intestinal transplantation, when the intestinal mucosa was actively regenerating, the demand for glutamine was markedly enhanced. The enhanced demand for glutamine was met by increased output of glutamine by the liver and skeletal muscle. Glutamine uptake by the intestinal graft was enhanced by a brief infusion of glutamine. Thus, we believe exogenous glutamine supplementation may be beneficial for the recovery of intestinal grafts with severe mucosal injury.