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Will Tissue-Engineered Urinary Bladders Change Indications for a Laparoscopic Cystectomy?
Tomasz Drewa, Piotr Chlosta and Rafal Czajkowski SURG INNOV 2010 17: 295 originally published online 23 July 2010 DOI: 10.1177/1553350610375092 The online version of this article can be found at:

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bladder resection and urinary diversion. Laparoscopic radical cystectomy (LapRC) is surgically advanced and is an extremely difficult technique. LapRC with tissue-engineered urinary diversion could become a management of choice for muscle invasive bladder cancer. FEBU. LapRC is a considerably less-invasive procedure compared with open radical cystectomy. MD. PhD1 Surgical Innovation 17(4) 295–299 © The Author(s) 2010 Reprints and permission: http://www. regardless of the kind of urinary diversion. Karlowicza 24. 2011 . which in spite of this. the procedure is continued with sectioning 1 2 Nicolaus Copernicus University. and radical prostatectomy). pouch or neobladder) when performed during laparoscopy necessitates a conversion to open procedure.3 and Rafal Czajkowski. Then. pyeloplasty. the procedure starts with dissection of seminal vesicles and the posterior surface of the prostate. PhD. Keywords laparoscopic radical cystectomy. PhD.nav DOI: 10. MD. including oncology (radical nephrectomy.2-4 The urinary diversion technique using autologous bowel is associated with substantial extension of the operative time and higher complication rates. Laparoscopic radical cystectomy (LapRC) is surgically advanced and is an extremely difficult technique but presents many advantages. Urinary diversion using an autologous bowel is associated with longer operative times and complications.6 Laparoscopic Radical Cystectomy: The Technique Procedures are comparable between authors. uretherolithotomy. PhD.1 Laparoscopy is regarded as a standard operation access in almost all procedures in urology. and it could be completed within an acceptable at CALIFORNIA DIGITAL LIBRARY on June 19. Ureters are divided. urinary diversion. Bydgoszcz. Poland Email: tomaszdrewa@wp. that is. MD. 85-092 Bydgoszcz.11 Bladder Resection Part In men. tremendous development in the field of tissue engineering and techniques of in vitro construction of urological organs may help overcome this barrier.1.1177/1553350610375092 http://sri. Poland Corresponding Author: Tomasz Drewa. Urinary diversion ( such as good pathological and clinical outcomes. FEBU. On the other hand. Recent clinical research demonstrated the feasibility of bladder wall regeneration supported using in vitro techniques. Tissue engineering techniques used for urinary diversion after cystectomy shorten the operative time and help avoid serious complications related to bowel surgery. ligation of varicocele. Institute of Oncology. Kielce. adrenalectomy. Nicolaus Copernicus University. tissue engineering Introduction Open radical cystectomy is a “gold standard” treatment of muscle invasive urinary bladder cancer. Tissue Engineering Department. Bydgoszcz. MD. Poland 3 Department of Urology. ul. The authors have analyzed the LapRC procedure and its 2 main parts—that is.7-11 The technique used by our team begins with the creation of 5 ports for 2 trocars of 5 mm and 3 trocars of 10 mm. Poland Institute of Oncology. bowel Downloaded from sri. FEBU.sagepub.Will Tissue-Engineered Urinary Bladders Change Indications for a Laparoscopic Cystectomy? Tomasz Drewa. with one exception—radical cystectomy.2 Piotr Chlosta. The emphasis was on the operative time and complications related to the urinary diversion procedure. sagepub.sagepub. open radical Abstract Radical open cystectomy is a treatment of choice for muscle invasive urinary bladder cancer. but the operative time is still long. A urinary diversion created in vitro could make the LapRC totally intracorporeal. and bladder ligaments and vessels are supplied with clips.5. presents many advantages.

and in the case of tissue-engineered device implantation. and appropriate cell amount for reconstruction of such a huge organ like the human bladder. and only small clinical series can be found in the literature. and therefore data are lacking. Maffezzini et al25 have noticed in a group of 107 patients that 26% who underwent radical cystectomy with intestinal urinary reconstruction experienced complications. Future Perspective We have analyzed the time for the LapRC procedure and its 2 main parts—that is. if the total operative time was shorter than that for the open procedure and the whole procedure could be performed intracorporeally. Engineering (in vitro creation) of a neobladder from autologous urothelial and smooth muscle cells cultured on biocompatible—either synthetic or naturally derived—substrates is now feasible. incision of pelvic fascia. The postoperative specimen is removed together with lymph at CALIFORNIA DIGITAL LIBRARY on June 19. pouches. and anterior vaginal wall is removed transvaginally. Urinary Diversion Part Two kinds of urinary diversions are preferable after radical cystectomy for bladder cancer: the first one is a urinary orthotopic neobladder sewed from the bowel segment. dissection of the apex.15 An artificial bladder wall created in vitro was used for the first time in patients needing cystoplasty. Tissue-Engineered Urinary Diversion After Bladder Removal It was shown that implantation of a polymer scaffold seeded with autologous bladder cells did not show significant local or systemic toxicity.14 It is clear that there is a need to obtain such tissue-engineered artificial bladders. Bowel complications were the major cause of death following salvage cystectomy. and conduits for urinary diversion after LapRC.7% after salvage cystectomy. adnexes. After closing the vagina. clinical practice says that costs can be lowered only if the innovative technique works in properly selected patients.sagepub.11 The emphasis was on the operative time and complications related to the urinary diversion procedure. Only 7 bladders were augmented in humans with the tissue-engineered bladder wall. In women.17 Alberti and colleagues suggested a creation of simple structures like tissue engineered conduit or continent pouch when waiting for success with complete tissue-engineered bladder with a trigone-shaped base. with minor and major complications in 26% and 11% of patients. Future research should examine whether a tissue-engineered artificial conduit or artificial neobladder for urinary diversion could help shorten the operative time for LapRC.16 We should keep in mind that hospital procedures are covered by insurance companies.24 the total complication rate was 34%.23 Bowel complications were the major source of early morbidity after primary and salvage cystectomy. Ureters are anastomosed to an ileal conduit or the urinary neobladder. It is created via laparotomy but grafted using a pure laparoscopic technique. Surgical Innovation 17(4) for humans. it would probably be very expensive. and sectioning of urethra.22. lymph nodes are removed. It has to be emphasized that tissue engineering is a growing discipline. such as the Atala Group.13 This study suggests that such tissue-engineered neobladders are safe and effective for reconstructive surgery. We have established the potential benefits associated with an autologous urinary diversion ex vivo created for cystectomized patients.23 In the analysis by Boström and coworkers. On the other hand. the procedure starts with dissection of uterus ligaments and the peritoneum in the Douglas cavity.16.19-21 The human model is still a challenge reserved only for teams with a lot of financial support. which Downloaded from sri. Urinary leakage occurred in 3% following radical cystectomy and 8. Artificial conduits for urinary diversion in a small animal model were constructed. 2011 . but this procedure remains complex with potential complications. The neobladder is formed using absorbable running sutures from the prepared bowel segment.22 Open radical cystectomy is still the fastest method of bladder removal for muscle invasive cancer (Figure 1). The bowel segment for urinary diversion is divided. which are performed via an open laparotomy technique. The main drawbacks of tissue engineering are costs of cells expanding in vitro.296 of the Retzius space. LapRC is a very involved procedure. uterus.and medium-sized animals are both models in which bladder reconstruction is feasible and reasonable from the economical point of view.17 We are still waiting for the results of the phase II clinical trials on tissue-engineered human urinary bladders. The bladder with the urethra. Bowel ends are anastomosed using staples or running sutures. Urinary conduit made from the bowel is connected to the abdominal wall.18 Our experience is in line with the opinion of other scientific groups that small.16 The development of an artificial neobladder would warrant the prevention of both the metabolic and neoplastic shortcomings of the intestinal neobladder as well as early complications after cystectomy and urinary diversion.17. We think that LapRC would be a management of choice for muscle invasive bladder cancer. and the second is a bowel conduit.12.16 No tissue-engineered conduits were prepared Discussion Radical cystectomy has become the best form of therapy for invasive bladder cancer. the bladder resection part and urinary diversion part performed in our department.14. respectively. cell senescence during culture.

this appears to be feasible (Figure 2). after laparoscopic removal of the bladder. The time for orthotopic neobladder creation (urinary diversion part) is almost 4 hours (3. 2011 .3-3.26 In our series of 47 patients. 43 procedures were performed laparoscopically.27 Our experience with open and LapRC techniques shows that the operating time is a crucial factor influencing the choice of method of treatment.6%. it has to be emphasized that the mean operative time for the laparoscopic procedure.0).7%. One has to shorten the time for the urinary diversion procedure.8 hours (1. based on our experience. a short-term paralytic ileus was found on the second day after surgery. as reported by Hemal et al. cannot be completed intracorporeally. minimally invasive techniques have been used for both the extirpative as well as the reconstructive portions of the procedure. Stress has to be laid on the fact that a short time of bladder resection does not guarantee a short time for the whole procedure of LapRC (Figure 2). the complication rate related to the bowel can be minimized theoretically to zero. and because of this. respectively. The time for cystoprostatectomy and lymphadenectomy (bladder resection part in men) was 1. was longer (Figure 1). 297 and open radical cystectomy performed for bladder cancer.2).8. the procedure time can be substantially shortened (Figure 2).7 hours). Tissue-engineered constructs used for urinary diversion can really shorten the operative time and help omit bowel complications.27 It can be concluded that bowel complications although not frequent should still be taken into consideration when cystectomy is offered as a treatment choice.5-4.9 It should be mentioned that this study was undertaken by a leading center in laparoscopic surgery.4 (robot assisted) by Murphy et al. One patient developed leakage of ileal anastomosis on the sixth day after the operation. The total operative time of LapRC is similar when comparing between centers. that the time taken for the bladder resection part is now as short as possible. but in 4 cases. An artificial bladder wall created in vitro was used in clinical experiments Figure 1. open technique was necessary. or sepsis requiring reexploration developed in 29% of patients in the series presented by Haber and colleagues.7 hours (2.28 When comparing the results of laparoscopic Downloaded from sri. The time for conduit creation (urinary diversion part) was 2.1 ± 1.3-2. in fact.10.23 Murphy et al8 presented a mean operative time of 6.sagepub. Artificial and prepared in vitro conduit or neobladder allow spare bowel continuity.8. The patient was operated successfully using the laparotomy technique. bowel obstruction.11. even combined with extracorporeally created urinary diversion.4% and 2. In 6 cases.11 Ramani et al27 have stated that the contemporary standards for 1. The mean operative time of LapRC and extracorporeal urinary diversion was 5.8 and pure laparoscopic procedure (pure laparoscopy) where all parts of the procedure were performed intracorporeally by Deger et al9 led to relaparotomy in 10% of patients.0).8 (4. but it has to be shortened. We think. Urinary diversions with robot-assisted radical cystectomy are performed extracorporeally via a small incision because the intracorporeal procedure involves a long operative time with associated morbidity and complications.10 Postoperative ileus was observed in 23% of patients who underwent radical cystectomy with urinary diversion in the study presented by Park and coworkers.4 hours for robotic-assisted LapRC and extracorporeal urinary diversion. LapRC is associated with morbidity largely resulting from the urinary diversion procedure. The future of pure LapRC (including robot-assisted procedures) with intracorporeal reconstruction of the urinary tract using bowel segments does not look so optimistic.5-5. and considering all aspects of the procedure.8 Deger and collegues9 presented 12 patients who received rectosigmoid pouches for urinary diversion performed completely laparoscopically (entire procedure was intracorporeal).25 Anastomotic at CALIFORNIA DIGITAL LIBRARY on June 19.4 They noticed that extracorporeal urinary diversion decreases the operating time while maintaining the benefits of laparoscopic surgery.1. and nothing revolutionary can be done regarding this part of the operation. The mortality rate was 3. The mean operative time of selected methods of cystectomies: an open procedure (open) according to Porpiglia et al. it has been associated with significant increases in operative times and perioperative complications.7. The median operating time was more than 8 hours (Figure 1). We have analyzed the operative time for LapRC.9 The usual method is performing the urinary diversion portion of the procedure extracorporeally. Sigmoid colon injury was found in 1 case but was treated by laparoscopic suturing.26 laparoscopic with extracorporeal creation of urinary diversion (laparoscopy [Lap] + open diversion) by Hemal et al.Drewa et al. conversion to the standard.2 hours. The time for cystohysterectomy and lymphadenectomy (bladder resection part in women) was 1.7.9.and 2-month mortality rates for radical cystectomy are 0.11 The mean time of the surgery in our cases was 4. In attempts to decrease the morbidity. Although a completely intracorporeal approach is technically feasible. We hypothesized that the tissue-engineered construct needs to be only sutured and because of this.2. because of technical difficulties. which.8 hours.

5 to 3 hours instead of 4. within reach of the surgeon. Stein JP.sagepub. create a urinary conduit. Mouzin M. This strategy will shorten the operative time and make it possible to perform the whole operation intracorporeally within an acceptable time. laparoscopy + bladder: laparoscopic cystectomy performed with extracorporeal neobladder creation. Kolla SB. It can be speculated that the procedure time could be reduced to 2. Guillotreau J. pouch.178:2340-2343. Comparison of laparoscopic and open radical cystoprostatectomy for localized bladder cancer with 3-year oncological follow-up: a single surgeon experience. 2. 3.17:369-375.5 hours (Figure 2). Curr Opin Urol. Gamé X. The urinary diversion part is the main reason for converting the procedure into an open one because of bowel preparation and dissection. All these advantages should prompt us to consider LapRC as a treatment of choice for muscle invasive bladder cancer in selected patients. 2011 . but LapRC is less invasive when compared with open radical cystectomy. Laparoscopy + TE conduit and laparoscopy + TE bladder are both hypothetical for cystoplasty. Open radical cystectomy with lymphadenectomy remains the treatment of choice for invasive bladder cancer. Operative times of laparoscopy + conduit and laparoscopy + bladder are real operating times. help avoid early and late complications related to bowel surgery. J Urol. J Urol. 2007. A tissue-engineered urinary bladder wall when used to construct a urinary diversion after urinary resection should allow LapRC to be regarded as a treatment of choice for muscle invasive bladder cancer. but the operative time is still too long for the urinary diversion part. and finally make the LapRC totally intracorporeal. Hemal AK. Hypothetical shortening of the operative time if tissue-engineered (TE) urinary diversions were used in the cystectomy procedure (laparoscopy [Lap]+ conduit: laparoscopic cystectomy performed with extracorporeal conduit creation. Tissue-engineered autologous conduits or neobladders created in vitro have several advantages: they facilitate performing LapRC in an acceptable amount of time. 2009. Huang GJ. Downloaded from sri. Radical cystectomy for bladder cancer: morbidity of laparoscopic versus open surgery. and this artificial (in vitro constructed) bladder wall can be used to References 1.298 Surgical Innovation 17(4) Figure 2. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the authorship and/or publication of this article. Conduits for urinary diversion can be constructed in a manner similar to that used for the artificial urinary bladder wall and can be used for laparoscopically cystectomized patients. 2007.181:554-559. or even the whole bladder and then used as a urinary diversion after LapRC. laparoscopy + TE bladder: laparoscopic cystectomy performed with tissue-engineered neobladder intracorporeal implantation). laparoscopy + TE conduit: laparoscopic cystectomy performed with tissue-engineered conduit implantation. The autologous urinary bladder wall was constructed in vitro and used in a human cystoplasty operation. et al. Conclusions Open radical cystectomy is a method of choice in the management of muscle invasive bladder cancer. Funding The author(s) received no financial support for the research and/ or authorship of this at CALIFORNIA DIGITAL LIBRARY on June 19. LapRC is surgically feasible.

2008. Kaznica A. Scaffold seeded with cells is essential in urothelium regeneration and tissue remodeling in vivo after bladder augmentation using in vitro engineered graft. 2009. Canepa G. Long-term durability.10:119-125.19:69-75. Dobruch J. Role of robot-assisted surgery for bladder cancer. Stein JP. 2009. 9. Downloaded from sri.10:243-255. 4.179:2035-2041. The artificial conduit for urinary diversion in rats: a preliminary study.39:1647-1651.65:905-908. Eur Urol. What’s in the pipeline about bladder reconstructive surgery? Some remarks on the state of the art. Colombo JR Jr. Tizzani A. 11. Ludlow JW. Roth CC. Wood at CALIFORNIA DIGITAL LIBRARY on June 19.38:133-135. 12. Fung KM. Alberti C. Deger S. Open versus laparoscopyassisted radical cystectomy: results of a prospective study. Urology. 2009. Boström PJ. 2008. 23. 5. Urology. Is pure laparoscopic radical cystectomy still an attractive solution for the treatment of muscle-invasive bladder cancer? [published online ahead of print April 8. Drewa T.1159/ 000310349. 2004. Current status of tissue engineering in urology. 10. et al. Parodi D. Haber GP. Park HK. Minerva Urol Nefrol. Regen Med. Buscarini M. Transplant Proc. Bromage SJ. Atala A.17:41-48. Challacombe BJ. Roboticassisted laparoscopic radical cystectomy with extracorporeal urinary diversion: initial experience. 2008. 18. Yoo JJ. Greco A. Campodonico F. 2007. Lin HK.21:325-329.71:41-46. 2007. Loening SA. BJU Int. Woźniak A. Soker S.Drewa et al. Hemal AK. Jain D. Lee SE. Laparoscopic radical cystectomy: current status. et al. Chlosta P. Billia M. Curr Opin Urol.41. Kwak C. 2009. Murphy DG. 28. Maffezzini M. 8. Clarke NW. Ramani VA. Complications of radical cystectomy. 14. Haber GP. Gill IS. 21. 2004. Drewa T. Curr Treat Options Oncol. 2005. Risk factors for mortality and morbidity related to radical cystectomy. Tissueengineered autologous bladders for patients needing cystoplasty. Int J Artif Organs.70:910-915. Frimberger D. 2007. 15. Porpiglia F. 19. Southgate J. Urol Int. 13. Retik AB. Local and systemic effects of a tissue engineered neobladder in a canine cystoplasty model. Gerbi G. Campbell SC. Kolla SB. an animal study. Elhage O. Kössi J. 2009. 6. BJU Int. Adamowicz A. Pielichowski J. Sir J. Perioperative outcomes with laparoscopic radical cystectomy: “pure laparoscopic” and “open-assisted laparoscopic” approaches. et al.81:330-334. Pasin E. 17. Czajkowski R. J Urol. Current perioperative management of radical cystectomy with intestinal urinary reconstruction for muscle-invasive bladder cancer and reduction of the incidence of postoperative ileus. Curr Opin Urol. Joachimiak R. Kropp BP. Lin HK. The use of tissue engineering and stem cells in bladder regeneration.sagepub. Bauer SB. 2007. 25. Campbell SC. J Tissue Eng Regen Med. Drewa T. Laato M. Urology. Nurmi M. 2008. J Endourol. 22. Primary cultures from rat vibrissae as potential cell source for in vitro construction of urinary bladder wall grafts. Kropp BP. 27. Peters R. Drewa T. Chitosan scaffold enhances nerve regeneration within the in vitro reconstructed bladder wall. Łysik J. 2008. 2011 . 54:570-580. 2009. Tuerk IA. Early removal of nasogastric tube after cystectomy with urinary diversion: does postoperative ileus risk increase? Urology. Lee E. A contemporary standard for morbidity and outcome after radical cystectomy.1:425-435. Sir J. Laparoscopic radical cystectomy with continent urinary diversion (rectosigmoid pouch) performed completely intracorporeally: an intermediate functional and oncologic analysis. doi:10. 2006. 20. outcomes. Sarafian V. Azzarello J. 2008. Hemal AK. Wadhwa P. 24. Curr Urol Rep. et al. Irwin BH. Drewa T. Wille AH. 2006. Polasik J. Urol Int. 2008.103:191-196. Renard J. Lancet. tissue regeneration and neo-organ growth during skeletal maturation with a neo-bladder augmentation construct. Surg Oncol. Transplant Proc.367:1241-1246. et al. Transplant Proc. Regen Med. 7. Recent advances in urologic tissue engineering. Atala A.104:628-632. 2010].18:564-569. 2006. Roigas J.59:67-87. Yoo JJ. and patient selection. Piovano M. Laparoscopic radical cystectomy and extracorporeal urinary diversion: a single center experience of 48 cases with three years of follow-up.27: 737-743. 26. Age-dependent vascular endothelial growth factor expression and angiogenic capability of bladder smooth muscle cells: implications for cell-seeded technology in bladder tissue engineering. 2009. Jayo MJ. Kropp BP. Dogra PN.3:671-682. Byun SS. Gupta NP. 299 16. Kwon TG.3:579-589.64:935-939.