”Chinese Journal of Pediatric Surgery, Vol. 3, 2012
The repair of long-segment urethral strictures or urethral defects remains a major challenge in urology, especially the lack of ideal urethral replacement materials after multiple surgeries. The materials available for urethral repair in clinical practice include patients’ autologous materials, cultured uroepithelial cells in vitro and artificial materials. However, more or less all of them have some problems. We tried to use human allogeneic dermal decellular matrix made by tissue engineering technology from March 2010 to April 2011, and applied it as an alternative material for urethral reconstruction in clinical practice, and observed the preliminary clinical results in comparison with related literature, which are reported below. Yu D, Department of Pediatric Surgery, Jinan Children’s Hospital
1.Clinical data.
There were 16 male children in this group, aged 2-8 years old, including l2 cases with penile corporal hypospadias, 2 cases with long segmental urethral fistula (1 cm) after hypospadias surgery, and 2 cases with urethral stricture (1 case with posterior urethral stricture due to pelvic fracture urethral rupture and 1 case with repeated urethral dilatation without improvement for half a year after hypospadias surgery). The length of urethral defect was determined by preoperative retrograde urethrocystography in children with urethral stricture.
2.
Decellularized dermal matrix (AMG) material: produced by Beijing Qingyuan Weiye Biological Tissue Engineering Technology Co.
The patches were removed intraoperatively and rinsed 3 times with saline. Cut and apply according to the intraoperative urethral defect, and the thickness is generally 1 mm.
3. Methods.
(1) Urethral reconstruction method: 12 children with penile corporal hypospadias were treated with the Onlay method of preserving the urethral plate by making a U-shaped incision around the urethral orifice, anterior to the head of the penis and deep to the superficial layer of the white membrane, separating and preserving the urethral plate skin strip of appropriate width, cutting the allogeneic decellularized tissue patch to slightly wider than the preserved urethral plate skin strip, interrupted suturing with the preserved urethral plate with 6-0 PDS absorbent suture in a capped manner, and then Suture both sides of the fascia cover, separate the head of the penis both wings of the penile head shaping, if combined with mild penile recurvature can be corrected by decapping the penile skin and tightly suturing the dorsal white membrane of the penis, and finally cut the penile skin wrapping suture. In children with urethral stricture, in one case, the urethral stricture section was excised until the normal urethral mucosa was seen, and the surrounding scar was excised as completely as possible, the cut and prepared AMG was repeatedly flushed with saline three times, the AMG was sutured into a tube, and the two ends were sutured with the proximal and distal urethra with normal mucosal muscle with 6-0 PDS absorbable thread tension-free end-to-end anastomosis sutured with 6-8 stitches, the muscle The muscle, subcutaneous tissue, and skin were then sutured layer by layer, and wound drainage was left in place. In another case, the stenotic segment of urethra was incised to remove part of the scar tissue to anastomose with the preserved part of the urethra in a capped fashion. The F8-10 urethra was left in place as a stent, and the urethra was removed 3 to 4 weeks after surgery. In children with urethral fistula, the free urethra was incised along the edge of the fistula, the scar tissue was removed, and the AMG was cut according to the size of the defect and repaired with a lid, and then sutured in layers. The length of the reconstructed urethra was 1.5
cm – 4 cm.
(2)
Observation items: pay attention to keep the catheter unobstructed, observe the blood flow of the penile head, pack the dressing change to expose the wound 1 week after surgery, observe any local infection, rejection reaction, and survival of the graft; remove the catheter 3-4 weeks to observe the urination, any difficulty in urination and urethral fistula. Two children with long urethral defects were selected for cystoscopic observation of urethral epithelial growth at 6 months after surgery.
Results
All 16 children did not have any infection or rejection reaction, and all of them resumed normal urination after removal of catheter. Cystoscopy revealed that the new urethral canal was normal.
Discussion
The treatment of long-segment urethral strictures and defects is a difficult problem for urologists, and at present, skin pieces or flaps from the patient’s own genital area and outside the genital area, such as scrotal tipped skin tubes, foreskin and abdominal flaps, are often used clinically to repair the strictured urethra, which is complicated and technically demanding, and there are still complications such as necrosis of the grafted flap, scrotal skin hair production, contraction and stricture of the grafted piece, stone and diverticulum formation, etc. complications, and the site and extent of the grafting is also limited. From the results, the use of autologous tissue implantation to treat urethral strictures also only maintains the continuity of the urethra and lacks urethral epithelium after repair, so it is not yet a functional repair. Mucosal skin slides often use buccal mucosa, labial mucosa, or bladder mucosa, but they are less commonly used clinically due to glandular secretion and complications in the donor area, and testicular sheaths and peritoneal skin slides often cause contracted strictures. And the use of uroepithelial migratory cells, cell culture on the scaffold, and then placed into the human body, need to take the bladder mucosa before the urethral reconstruction surgery, the surgery is traumatic, the operation is complicated, and the cell culture technology is demanding, which is not conducive to the large-scale clinical application. The use of artificial non-degradable materials such as polysilicon and polytetrachloroethylene exist for tissue necrosis, fistula, stricture, extravasation, stone formation, etc.; L-type polylactic acid (PLLA) polyhydroxyacetic acid (PGA) and other degradable artificial materials as scaffolds for urethral epithelial culture (1)
, although easy to take and easy to prepare, the inflammatory reaction is heavy in the process of degradation, which affects the differentiation and proliferation of cells and cannot interact ideally with cells, which is not conducive to the repair of the urethra, and the safety of polymeric biomaterials is still under doubt.
In fact, tissue engineering techniques have been applied earlier in the treatment of urethral repair. shokeir et al. (2) investigated the feasibility of repairing the urethra with tubular decellular matrix by replacing the urethra of dogs with biomaterials and showed that the results were not satisfactory for urethra with a defect of more than 3
cm, the results were unsatisfactory, with complications such as graft constriction, reconstructed urethral strictures, and fibrosis.
Sievert et al. (3) extracted homogeneous rabbit urethra to make AMG and completed rabbit urethral repair at 10
Urodynamic, urographic and histological studies between 10 d and 8 months revealed no rejection of the graft and good epithelial growth with vascular ingrowth on histological examination. It is believed that homogeneous AMG can perform stage I urethral reconstruction without complications, and this reconstruction is a functional histological regeneration.
In China, Liu Liu et al. (4) conducted experiments on the reconstruction of the canine urethra with allogeneic dermal AMG, and also achieved satisfactory results, and performed two cases of successful clinical application of human urethra.
Based on the success of animal experiments, Atala et al.(5)
In four children with failed conventional surgical treatment for hypospadias, their urethral defects were repaired with human AMG. 1 year after surgery, urethrography showed no strictures and cystoscopy revealed a normal lumen of the new urethra, and histological and immunocytobiological examination of the biopsies taken showed typical urethral epithelium formation. At 3 years of follow-up, all but one case with a new urethra of 15
The results were satisfactory, except for one case with a new urethra of 15 cm, in which a fistula under the head of the penis was observed.
On this basis, EL-Kassaby et al. (6) repaired 28 adult urethral strictures with the same material; 24 cases were successful, 4 cases had mild strictures at the urethral anastomosis, and 1 case had a subcoronal urethral fistula that resolved spontaneously after 1 year.
Kassaby et al. (7) reported on 6O children with hypospadias and adults with urethral strictures who underwent urethral reconstruction with an inert submucosal matrix of the bladder. The newly constructed urethra was 1.5 to 16.0
Urethrography and cystoscopy were performed 4 months after the operation, and the new urethra was found to be indistinguishable from the normal urethra in appearance. Subsequently, 3O patients with urethral strictures were selected for a randomized controlled trial of oral mucosal graft reconstruction of the urethra and decellularized bladder matrix graft reconstruction of the urethra (8), and the results showed that good results were achieved with decellularized bladder matrix grafts in urethral reconstruction, and normal urethral mucosal tissue was formed after surgery.
Extracellular matrix has the advantages of small species differences, weak antigenicity, less likely to trigger immune rejection by the host, good biocompatibility and better biodegradability. It is an ideal biological scaffold that can produce functional new organs, which is not achieved by other artificial materials or natural polymer materials, and can effectively solving the problem of insufficient donor materials for the host itself
It can effectively solve the problem of insufficient donor material for the host.
In our group, all 16 cases of AMG implantation were viable and no rejection occurred. All of them were followed up from 3 to 6 months after the surgery. All children were able to urinate normally through the urethra, and three children developed urethral strictures and underwent regular urethral dilatation or incision. In the surgical operation, only the urethral defect segment was isolated and sutured with a cover or AMG sutured into a tubular replacement defect, which can ensure a completely tension-free anastomosis and a simple surgical operation. This repair is anatomic and functional. Thus, compared to conventional urethral replacement materials, this material has the following advantages: (1) No autologous material is required, reducing patient pain;
(2) low antigenicity and fewer complications; (3) the repaired urethra has similar tissue structure and physiological characteristics as the original urethra; (4) it greatly simplifies the surgical procedure. the cure rate of stage I molding is similar to that of traditional surgery. From the observation of the treatment effect of this group, in the repair of urethral defects, the time to complete the repair relying on autologous urethral cell growth is related to the length of urethra, and the time to complete the repair is relatively long for long distance defects, especially those over 4 cm. However, homogeneous dermal AMG is a “free graft” after all, so it cannot avoid the problem of contracture and restenosis after repairing the urethra, and reconstruction of the urethra by “capping” should be better than tubular urethral replacement. However, the preliminary clinical results confirm that human allogeneic dermal AMG is an ideal alternative urethral replacement material.
References
1. 0lsen L, Bowald S, Busch C. et a1. Urethral reconstruction with a new
sythetic absorbable device.Scand J Uml Nephrol, 1992, 26: 323_326.
2. Shokeir A,0sman Y. Acellular matrix tube for canine urethral
replacement: is it fact or fiction[J] J Urol, 2004, 171(1):453- 456.
3. Sievert K, Bakireioglu M , Nunes L, et a1. Homologous acelular matrix graft
for urethral reconstruction in the rabbit: histological and functional
evaluation.J Urol, 2000, 163: 1958-1965.
4. Liu Liu, Liang DJ, Shen PF, et al. Experimental and clinical study of allogeneic dermal extracellular matrix reconstruction of the urethra. Chinese Journal of Urology, 2001, 22: 428_43
5. Atala A , Guzman L, Retik AB. A novel inert collagen matrix for hypospadias
repair.J Urol, 1999, 162(3 Pt 2):1148-1151.
6. el Kassaby AW , Retik AB, Yoo JJ, et a1.Urethral stricture repair with an
off-the-shelf collagen matrix.J Urol, 2003, 169(1):170-173.)
7.Kassaby EA , Yoo JJ, Retik AB, et a1.A novel inert collagen matrix for
urethral stricture repair.J Urol, 2000, 163(Suppl 4):70-71.
8. el Kassaby A , Aboushwareb T, Atala A. Randomized Comparative Study Between
Buccal Mucosal and Acellular Bladder Matrix Grafts in Com plex Anterior U
rethral Strictures[J].J Urol, 2008, [Epub ahead of print]