Articles

Re: Tissue-Engineered Autologous Urethras for Patients Who Need Reconstruction: An Observational Study

By: Guido Barbaglia and Massimo Lazzerib lowast

Published online: 01 December 2011

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Raya-Rivera A, Esquiliano DR, Yoo JJ, Lopez-Bayghen E, Soker S, Atala ALancet 2011;377:1175–82Experts’ summary:In this investigative pilot study, the authors reported the effectiveness of tissue-engineered urethral tabularised posterior urethroplasty, using the patients’ own cells, for five boys (median age: 11 yr; range: 10–14 yr). To validate the long-term efficacy and rule out restrictures, Raya-Rivera and colleagues followed up patients for a median of 71 mo (range: 36–76 mo). All the engineered neourethras were implanted without any severe intraoperative complications, and no significant postoperative complications such as fistulas or urinary tract infections were reported. Functional objective evaluation showed a median maximum urinary flow rate of 27.1ml/s, and imaging, serial radiographic voiding cystourethrography, and endoscopic studies revealed the maintenance of wide urethral calibres without any recurrent stenosis. The authors performed a urethral biopsy follow-up, showing the development of a normal-appearing architecture by 3 mo after implantation. They concluded that urethral structures can be engineered and will remain functional in a clinical setting for a long period in a paediatric population. The innovation was that tissue-engineered urethras, created with the patients’ own cells and having histologic and functional characteristics similar to native urethras, can be used to successfully treat complex urethral defects. Tissue-engineered urethras could be a new alternative source for reconstruction in the armamentarium of urologists.Experts’ comments:The authors, who were the first to report successful posterior urethra reconstruction with tissue-engineered urethras using the patients’ own cells for the treatment of traumatic strictures, should be commended for their success in translating basic research into clinical application. They have to be praised for choosing a homogeneous, although small, group of patients (male paediatric subjects with similar strictures in the same location) and for the extension of follow-up. The remarkable gain in life expectancy in developed countries stands out as one of the most important achievements of the last century, and most babies born in the year 2000 or afterwards in Western countries will celebrate their 100th birthdays. Consequently, we will operate on more and more paediatric patients with urethral or penile defects who will live longer, and our results need to be durable over time. Extending follow-up becomes essential if we are to know, and not just wonder, how tissue-engineered urethral reconstruction holds up over time. Long-term follow-up is the main factor affecting the validity of efficacy and the safety of treatments for urologic disease using stem cells. We encourage the authors to follow these patients and give us further updates. Finally, this work could open the way for the use of adequately long collagen–polyglycolic acid scaffold tubes seeded with autologous urothelium and muscle cells for the reconstruction of longer anterior strictures and treatment of panurethral disease.

Surgical treatment of urethral stricture diseases is a continually evolving process, and there is renewed controversy over the best means of reconstructing the urethra, as the superiority of one technique over another has not yet been clearly determined [1]. Notwithstanding, the use of tubes for urethral reconstruction has been abandoned, and end-to-end anastomosis and one-stage flap or graft urethroplasty have become the gold standard for the treatment of most urethral strictures [2] and [3]. The future is at the door, and the tissue-engineering material for urethral reconstruction is already available. Several questions remain unanswered: How should we use this new grafting material? Should we use a tube or a graft? Should we use the onlay or the inlay technique? These questions are not negligible. The inlay graft technique designs a bed between two strips of original urethral mucosa where you might place the tissue-engineered material. When the new epithelial tissue–engineered material is closely placed between two urethral mucosa epithelial strips, how will the incorporation, the re-epithelisation, and the transformation of the transplant tissue into urethral mucosa result?

There is a grey zone between research and practice when we introduce innovation into the theatre, and although we do not want to suffocate surgical innovation, we also must not forget the safety of patients in the development of new operations. Because the safety and proof of concept in human beings are the main goals at this stage, we suggest that very few highly skilled surgical teams should be involved in tissue-engineered urethra reconstruction, and that their example should have a substantial effect on the diffusion of the technique. Few patients have to be recruited; they should be selected for specific characteristics and under a severe regulatory process.

We are looking at advances in urethral reconstruction with the hope that in the laboratory we might one day grow individually customised biologic urethra replacements for patients. Of course, such a revolutionary technique might sooner or later face cuts in expenditures on health care resulting from economic conditions, and we have a substantial way to go before such a dream is to be realised. However, there is room for hope.

Conflicts of interest

The authors have nothing to disclose.

References

  • [1] S.B. Kulkarni, G. Barbagli, J.S. Kulkarni, G. Romano, M. Lazzeri. Posterior urethral stricture after pelvic fracture urethral distraction defects in developing and developed countries, and choice of surgical technique. J Urol. 2010;183:1049-1054 Crossref.
  • [2] G. Barbagli, G. Morgia, M. Lazzeri. Retrospective outcome analysis of one-stage penile urethroplasty using a flap or graft in a homogeneous series of patients. BJU Int. 2008;102:853-860 Crossref.
  • [3] G. Barbagli, M. Lazzeri. Surgical treatment of anterior urethral stricture diseases: brief overview. Int Braz J Urol. 2007;33:461-469

Footnotes

a Center for Reconstructive Urethral Surgery, Arezzo, Italy

b Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy

lowast Corresponding author.