EUROPEAN UROLOGY 60 (2011) e21–e22 available at www.sciencedirect.com journal homepage: www.europeanurology.com Letter to the Editor Reply to Declan G. Murphy, Thomas J. Walton, Paul J. Cathcart, et al’s Letter to the Editor re: Bayan Alsaid, Thomas Bessede, Djibril Diallo, et al. Division of Autonomic Nerves Within the Neurovascular Bundles Distally into Corpora Cavernosa and Corpus Spongiosum Components: Immunohistochemical Confirmation with Three-Dimensional Reconstruction. Eur Urol 2011;59:902–9 We thank Murphy et al. for their comments on our paper [1]. Their letter raises important questions regarding our methodology and results. We appreciate their interest in our work and the opportunity to respond to their concerns. Indeed, many of the mentioned points were clarified during the revision procedure through reviewer comments. We would mention that our study is not only a quantification study; the quantification study was made to facilitate the description of our three-dimensional (3D) reconstruction. The first point for clarification is our methodology beyond the prostate apex. The quantification study was made in the three levels of the prostate: base, mid, and apex. At the beginning of our study, quantification was also attempted at the level of membranous urethra (beyond the prostate), but at this level, the nerve fibers from the pudendal nerve innervating the urethral sphincter intermingled with the autonomic nerve fibers and made precise quantification difficult at the selected level. For this reason, we did not include quantification beyond the apex. However, we followed the periprostatic nerve fibers distally to the apex in our serial immunolabeled sections, and we were able to describe their direction towards the corpora cavernosa and the corpus spongiosum. To clarify the nature of those nerves, an immunohistochemcal study was recently performed using the neuronal nitric oxide synthase (nNOS), anti–vesicular acetylcholine transporter, and anti-tyrosin hydroxylase antibodies; the results in the fetus demonstrated the existence of nNOS-positive nerve fibers within both cavernous and corpus spongiosum nerves (unpubl. data), but the results in the adult specimens were nonsignificant (false negativity and false positivity) due to uncontrolled postmortal conditions affecting immune reactivity; further studies are required to clarify this point. In respond to the second question about fascial compartmentalization, we did not note fascial compartmentalization around the prostate, as described by Costello et al. [2], or beyond the prostate apex. Interindividual variation may explain our observation, and further studies are required with higher numbers of specimens. We used the term division to describe our two groups or bundles of nerve fibers with two different destinations. We would like to clarify an important point: Our illustrations are not computer reconstructions using Photoshop or graphic illustrations. Photoshop was used only to realign and regroup the histologic images. The reconstruction was made using WinSurf (SURFdriver Software) after manually outlining and following hundreds of nerve fibers in each subject. Moreover, not only was our description based on the 3D-reconstruction illustration, it was proved by the immunohistochemical demonstration. The repeated observation, when following the nerve fibers in the serial immunolabeled sections, was the origin of our findings. In Figure 3 of our paper [1], immunolabeled nerve fibers were followed in the two posterolateral and anterolateral positions with clear final destinations for both groups. In the adult, the complete reconstruction was made in two specimens (72 and 74 yr old), and partial reconstruction was made of the seminal vesicle of another cadaver specimen (72 yr). Figure 6 in our paper [1] is not a model from mean data but is a true reconstruction of all immunolabeled nerve fibers >20–25 mm, which were manually outlined in 100 levels (700 histologic sections using 70 standard cassettes from 25 transverse sections). The first complete reconstruction required 8 months to be achieved. We did not integrate the same views from the second complete adult reconstruction so as not to overcharge the article illustrations. To respond to the third clinical point concerning the importance of anterior nerve preservation, our description provides anatomic evidence supporting the new vision of nerve-sparing techniques, as described recently by Savera et al. [3] and Asimakopoulos et al. [4]. Most men regain only partial potency after nerve-sparing radical prostatectomy with regard to preoperative erectile function [5,6], and this is probably the reason for constant technical evolution [3,4,6,7] of the initial technique proposed by Walsh and Donker [8] in 1982. Our findings suggested that the number of nerves participating in the erection of the penis is probably higher DOIs of original articles: 10.1016/j.eururo.2011.02.031, 10.1016/j.eururo.2011.05.058 0302-2838/$ – see back matter # 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2011.05.057 e22 EUROPEAN UROLOGY 60 (2011) e21–e22 and that their distribution and nature are more complex than previously thought, explaining why not all men recover their preoperative erectile function, despite a well-done nervesparing technique. Conflicts of interest: The authors have nothing to disclose. [6] Nielsen ME, Schaeffer EM, Marschke P, Walsh PC. High anterior release of the levator fascia improves sexual function following open radical retropubic prostatectomy. J Urol 2008;180:2557–64, discussion 2564. [7] Lunacek A, Schwentner C, Fritsch H, Bartsch G, Strasser H. Anatomical radical retropubic prostatectomy: ‘curtain dissection’ of the neurovascular bundle. BJU Int 2005;95:1226–31. [8] Walsh PC, Donker PJ. Impotence following radical prostatectomy: insight into etiology and prevention. J Urol 1982;128:492–7. References [1] Alsaid B, Bessede T, Diallo D, et al. Division of autonomic nerves within Bayan Alsaid* Thomas Bessede the neurovascular bundles distally into corpora cavernosa and corpus Djibril Diallo spongiosum components: immunohistochemical confirmation with David Moszkowicz three-dimensional reconstruction. Eur Urol 2011;59:902–9. Ibrahim Karam [2] Costello AJ, Dowdle BW, Namdarian B, Pedersen J, Murphy DG. Gérard Benoı̂t Immunohistochemical study of the cavernous nerves in the peri- Stéphane Droupy prostatic region. BJU Int 2011;107:1210–5. [3] Savera AT, Kaul S, Badani K, et al. Robotic radical prostatectomy with Laboratory of Experimental Surgery, EA4122, Faculty of Medicine, University of Paris-Sud 11, Le Kremlin-Bicêtre, France the ‘‘Veil of Aphrodite’’ technique: histologic evidence of enhanced nerve sparing. Eur Urol 2006;49:1065–74, discussion 1073–4. *Corresponding author. Laboratoire de chirurgie expérimentale, [4] Asimakopoulos AD, Annino F, D’Orazio A, et al. Complete peripros- EA4122, Faculté de Médecine, Université Paris-Sud, tatic anatomy preservation during robot-assisted laparoscopic rad- 63 Rue Gabriel Péri, Le Kremlin Bicêtre, 94270 France ical prostatectomy (RALP): the new pubovesical complex-sparing E-mail address: drbayan@gmail.com technique. Eur Urol 2010;58:407–17. (B. Alsaid) [5] Audouin M, Beley S, Cour F, et al. Erectile dysfunction after radical prostatectomy: pathophysiology, evaluation and treatment [article in French]. Prog Urol 2010;20:172–82. May 31, 2011 Published online on June 12, 2011