Topographical Anatomy of Periprostatic and Capsular Nerves: Quantification and Computerised Planimetry

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1 available at journal homepage: Prostate Cancer Topographical Anatomy of Periprostatic and Capsular Nerves: Quantification and Computerised Planimetry Roman Ganzer a, *, Andreas Blana a, Andreas Gaumann b, Jens-Uwe Stolzenburg c, Robert Rabenalt c, Thorsten Bach d, Wolf F. Wieland a, Stefan Denzinger a a Department of Urology, University of Regensburg, Krankenhaus St. Josef, Regensburg, Germany b Department of Pathology, University of Regensburg, Regensburg, Germany c Department of Urology, University of Leipzig, Leipzig, Germany d Department of Urology, Asklepios Krankenhaus Barmbek, Hamburg, Germany Article info Article history: Accepted April 7, 2008 Published online ahead of print on April 15, 2008 Keywords: Capsular nerves Nerve-sparing Neurovascular bundle Periprostatic nerves Planimetry Abstract Background: The exact distribution of periprostatic autonomic nerves is under debate. Objective: To study the topographical anatomy of autonomic nerves of the periprostatic tissue and the capsule of the prostate (CAP). Design, Setting, and Participants: Whole-mount sections of 30 prostates from patients having undergone non nerve-sparing radical prostatectomy were investigated after immunohistochemical nerve staining. Sections from the base, the middle, and the apex were evaluated. All sections were divided into 12 sectors, which were combined into the following regions: ventral, ventrolateral, dorsolateral, and dorsal. Measurements: Quantification of periprostatic and capsular nerves was performed within the sectors. Computerised planimetry of the total periprostatic nerve surface area of each region was performed (Image-J software, Wayne Rasband, National Institute of Health, USA). Results and Limitations: A total of 3514, 3860, and 3902 periprostatic nerves was counted at the base, the middle, and the apex, respectively ( p = 0.068). The ratio of periprostatic nerves to capsular nerves was 3.6, 2.1, and 1.9 at the base, the middle, and the apex, respectively ( p = 0.004). Computerised planimetry revealed a significant decrease in total nerve surface area from the base over the middle towards the apex, with , , and mm 2 ( p = 0.004). The percentage of total nerve surface area was highest dorsolaterally (84.1%, 75.1%, and 74.5% at base, middle, and apex, respectively) but variable: Up to 39.9% of nerve surface area was found ventrolaterally and up to 45.5% in the dorsal position. The study is limited by the fact that autonomic nerve distribution was only investigated from the base to the apex of the prostate. Conclusions: Periprostatic nerve distribution is variable, with a high percentage of nerves in the ventrolateral and dorsal positions. Total periprostatic nerve surface area decreases from the base towards the apex due to nerves leaving the NVB branching into the prostate. This can only be discovered by nerve planimetry, not by quantification. # 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, University of Regensburg, Krankenhaus St. Josef, Landshuter Straße 65, D Regensburg, Germany. Tel ; Fax: address: roman.ganzer@gmx.de (R. Ganzer) /$ see back matter # 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eururo

2 Introduction Since the first description by Walsh and Donker of an anatomical radical prostatectomy involving a potency-sparing approach, urologists have long agreed that the neurovascular bundle (NVB) is located dorsolaterally on both sides of the prostate [1]. The exact distribution of periprostatic autonomic nerves is now under debate, however, since recent studies have revealed a wide variety of nerve distribution around the prostate [2 4]. It is not clear which of the periprostatic nerves finally contribute to erectile function and which of them at a certain point branch out into the prostate and other structures to regulate their physiology [5]. Exact understanding of the periprostatic neural anatomy is crucial in order to optimise potency-preserving approaches in radical prostatic surgery. We present a detailed topographical study of the distribution of periprostatic and capsular nerves. This is the first study in this field which combines systematic nerve quantification with computerised nerve planimetry in whole-mount sections after immunohistochemical staining. 2. Methods 2.1. Specimens All specimens were obtained prospectively from patients undergoing non nerve-sparing endoscopic extraperitoneal radical prostatectomy (EERPE) for biopsy-proven prostate cancer. Besides excision outside the periprostatic fascia, the aim of our technique was to maximize the margin of attached periprostatic tissue. Furthermore, attention was paid to ensuring that both layers of Denonvillier s fascia remained on the prostate. All procedures as well as the processing of the specimens were performed at one institution (University of Regensburg, Germany). The prostates were cut into slices of approximately 1.5 cm thickness to fit whole-mount preparation. They were fixed in 4% buffered formalin for 36 h and embedded in paraffin. Specimens were cut with a special microtome (HM 430, Microm International GmbH, Walldorf, Germany) into transverse serial whole-mount sections with a thickness of 10 mm. Histopathological analysis was performed on transverse whole-mount sections, whereas the most distal part of the apex was processed in sagittal direction according to the Stanford protocol [6]. Forourstudy,three consecutive whole-mount sections were prepared from the apex, the middle, and the base of the prostate, respectively. The seminal vesicles were not investigated in this study Staining methods Of the three consecutive sections of each region, one section was stained with hematoxylin-eosin (HE), whereas two sections were stained for prostatic nerve-fibres using a polyclonal antibody against the neural protein S100 (Dako, Hamburg, Germany). The specific immunohistochemical staining of autonomic nerves was confirmed by a single pathologist (AG) comparing selected pairs of HE and S100 sections Quantification of nerves The sections were digitised with a high-resolution flatbed photo scanner device (Perfection V750 pro, Epson, Meerbusch, Germany). For analysis, digital copies of each S100 whole-mount section were centrally covered with a raster dividing each whole-mount section into 12 sectors numbered clockwise [2] (Fig. 1A).In the first step,the stained nerves of each sector were counted, distinguishing between periprostatic nerves and nerves within the capsule of the prostate (CAP) (Fig. 1B). All further calculations were performed using mean values from the results of sectors of two adjacent S100 sections. The sectors were combined into the following regions: 12 and 1, ventral (V); 2 3 and 10 11, ventrolateral (VL); 4 5 and 8 9, dorsolateral (DL); and 6 7, dorsal (D) (Fig. 1B) Planimetry of total periprostatic nerve surface area The digitised whole-mount sections were processed with Image-J software (Wayne Rasband, National Institute of Health, USA). After defining a scale bar for each picture, they were converted to binary pictures in an automated routine. Planimetry of total nerve surface area was then analysed after surrounding the defined periprostatic regions manually [7] Statistical analysis Statistical analysis was performed with SPSS software, version 15 (SPSS Inc, Chicago, IL, USA). Differences between three independent variables were tested with the non-parametric Kruskal-Wallis test, with p-values of <0.05 considered statistically significant. 3. Results Specimens of 30 prostates were available for analysis. In all whole-mount sections used for this study, the CAP and the periprostatic tissue were intact and without artifacts. Baseline data of the patients and the specimens are shown in Table Quantification of periprostatic nerves Details of the periprostatic nerve distribution are shown in Table 2. In all specimens taken together, a total number of 3514, 3860, and 3902 nerves was counted at the base, the middle, and the apex, respectively, showing no statistically significant difference ( p = 0.068). In all whole-mount sections, the largest number of nerves was found in the

3 355 Fig. 1 Definition of regions for the quantification of periprostatic and capsular nerves and computerised planimetry of periprostatic nerves: (A) transverse whole-mount section of the prostate, immunohistochemical staining against S100 (V: ventral, VL: ventrolateral, DL: dorsolateral, D: dorsal); (B) magnification of box in A: capsular nerves (arrowheads) and periprostatic nerves (*). dorsolateral position. However, a considerable number of nerves was found to be located above the horizontal line (ventrolateral and ventral) as well as dorsal (Fig. 2A, B). At the base, the median number of nerves in the ventral position was significantly lower compared to the middle and the apex ( p < 0.001) Quantification of nerves of the prostatic capsule Details of capsular nerve distribution are shown in Table 2. The number of capsular nerves increased significantly from the base over the middle to the apex, with a total of 983, 1825, and 2057 nerves, respectively ( p < 0.001) Ratio of periprostatic nerves to capsular nerves The ratio of periprostatic nerves to capsular nerves proved to be significantly different between the Table 1 Baseline data Mean ( SD) age (yr) Mean ( SD) PSA (ng/ml) Mean ( SD) prostate volume (cc) Pathological T stage pt2a pt2c pt3a pt3b Median (range) Gleason score base, the middle, and the apex, with values of 3.6, 2.1, and 1.9, respectively, this factor being statistically significant ( p = 0.004) All details of the computerised planimetry of the periprostatic nerve surface area within the defined regions are shown in Table 3. In contrast to periprostatic nerve quantification, the overall measured surface of periprostatic nerves was statistically significantly different for the three regions, being highest at the base ( mm2), lower in the middle ( mm2), and lowest at the apex (89.50 mm2) ( p = 0.004). Details of the percentage of periprostatic nerve surface area are shown in Table 4. The largest surface of nerves was measured dorsolaterally, with 84.1%, 75.1%, and 74.5% at the base, the middle, and the apex, respectively. However, the distribution of periprostatic nerve surface area was variable, with a range of up to 39.9% ventrolaterally and up to 45.5% dorsally (Table 4) (3.3%) 14 (46.7%) 11 (36.7%) 4 (13.3%) 7 (5 9) Computerised planimetry of periprostatic nerves Discussion Recent studies on the periprostatic neural anatomy sustain a debate on how to optimise nerve-sparing techniques in radical prostatectomy [2,8,9]. Exact knowledge of the neuroanatomy of the prostate is

4 356 Table 2 Quantification of periprostatic and capsular nerves Periprostatic nerves Capsular nerves Periprostatic/capsular nerves Base Middle Apex p-value Base Middle Apex p-value Base Middle Apex p-value Ventral 38; 0.0 (0 11) 164; 3.8 (0 21) 122; 1.5 (0 24) < ; 0.0 (0 9) 84; 2.0 (0 21) 75; 1.0 (0 13) Ventrolateral 504; 12.3 (0 49) 667; 16.3 (0 51) 613; 16.5 (0 74) ; 3.0 (0 19) 348; 9.5 (0 27) 389; 9.0 (0 57) Dorsolateral 2587; 84.8 (24 149) 2685; 90.3 (27 152) 2550; 81.0 (32 148) ; 12.5(0 53) 1092; 37.0 (9 89) 1156; 33.3 (10 136) < <0.001 Dorsal 385; 7.0 (0 79) 344; 8.3 (2 37) 617; 12.5 (0 48) ; 4.5 (0 22) 301; 8.3 (1 36) 437; 9.5 (0 88) Total 3514; 10.8 (0 149) 3860; 14.8 (0 152) 3902; 17.5 (0 148) ; 3.0 (0 53) 1825; 8.8 (0 89) 2057; 9.8 (0 136) < All values in: total number; median (range). crucial in order to improve functional outcome after nerve-sparing radical prostatectomy. However, many anatomical and functional aspects of the nerves around the prostate remain unclear. In the current literature, several authors have described widely varying nerve distribution around the prostate, questioning the classical concept of a dorsolateral neurovascular bundle as described by Walsh and Donker [1,2,4,10]. However, so far it has not been possible to show exactly which nerves of the NVB contribute to erectile function and which part of these nerves contributes to the physiology of other structures. As long as the exact function of periprostatic nerves remains unclear, attempts should be made to preserve as much periprostatic nerve tissue as possible in nerve-sparing radical prostatectomy procedures, provided oncological safety is assured. In the present study, we performed a detailed topographical investigation of the periprostatic nerves after immunohistochemical staining of whole-mount sections of non nerve-sparing radical prostatectomy specimens. As a special feature, we also quantified the nerves within the CAP to obtain an indicator for nerves which leave the NVB, branch out into the prostate, and potentially do not support the physiology of erectile function. The quantification of periprostatic nerves revealed results comparable to other studies. In a study of 79 non nerve-sparing prostatectomy specimens, Kiyoshima et al could not confirm a bundle formation and observed a variation of the periprostatic nerve anatomy from case to case, with a nerve spread from the lateral aspect of the prostate to the apex in 52% of cases [11]. Lunacek et al demonstrated that the cavernous nerves are a distinct structure during the embryonic phase, but will be dispersed over the lateral prostatic surface with gestation [10]. Eichelberg et al showed that up to 28.5% of periprostatic nerves were located above the horizontal line [2]. The majority of nerves were found to be located dorsolaterally, with a median sum of 45.9%, 61.5%, and 65.6% of nerves at the apex, the middle, and the base, respectively. In our study, we were able to confirm the finding of periprostatic nerves being located mainly dorsolaterally. Furthermore, the median percentage of nerves was also highest at the base, with a mean percentage of 84.1% of nerve surface area dorsolaterally. Our findings revealed a strong variation of nerve spread, with up to 39.9% of nerve surface area being located ventrolaterally. Eichelberg et al performed their nerve quantification in wholemount sections stained with HE [2]. The special feature of our study was a nerve quantification in whole-mount sections after immunohistochemical

5 357 Fig. 2 Distribution of periprostatic nerves. Transverse whole-mount sections of the prostate from the apex (A) and the middle (B). Magnifications: (C) dorsal periprostatic and capsular nerves at the apex; (D) ventrolateral periprostatic nerves in the middle. staining, followed by computerised planimetry of the total nerve surface area in clearly defined periprostatic regions. Furthermore, we distinguished between periprostatic nerves and nerves within the CAP. Although immunohistochemical nerve staining is not necessarily required in order to count nerves accurately, it facilitates nerve identification and computerised planimetry of total nerve surface area. The shortcoming of simple nerve quantification is that this method fails to take into account the size of small and big nerves within the periprostatic tissue. Therefore, we combined nerve quantification with computerised planimetry of the total nerve surface area in Table 3 Computerised planimetry of periprostatic nerves Base Middle Apex p-value Ventral 0.391; ( ) 1.748; ( ) 1.462; ( ) Ventrolateral ; ( ) ; ( ) ; ( ) Dorsolateral ; ( ) ; ( ) ; ( ) <0.001 Dorsal ; ( ) 7.353; ( ) ; ( ) Total ; ( ) ; ( ) ; ( ) All values in: total; median (range) (mm 2 ).

6 358 Table 4 Distribution of periprostatic total nerve surface area Base Middle Apex Ventral 0.2% (0 1.4) 1.3% (0 7.6) 1.6% (0 20.6) Ventrolateral 7.0% (0 27.5) 18.1% ( ) 12.6% ( ) Dorsolateral 84.1% ( ) 75.1% ( ) 74.5% ( ) Dorsal 8.7% (0 32.2) 5.5% (0 18.4) 11.3% (0 45.5) All values in percentage of total nerve surface area (range). defined regions. This approach revealed interesting insights into nerve distribution around the prostate. The total number of quantified nerves alone showed no statistically significant difference between the base, the middle, and the apex ( p = 0.068). However, the total nerve surface area measured by computerised planimetry revealed a significant difference, with the largest nerve surface area to be found at the base, decreasing towards the apex ( p = 0.004). How can these findings be interpreted? Several authors support the concept that autonomic nerve fibres of the NVB spread out into the prostate and other structures and do not contribute to erectile function [12 14]. Costello et al studied the NVB in 12 fixed human male adult cadavers after microdissection and reported on nerve fibres innervating the prostate, the levator ani muscle, and the rectum [12]. Comparable to our study, they found a decreasing nerve density of the NVB as it courses distally along the prostate. The authors explained this fact by the innervation of the abovementioned structures. Due to the investigation of postprostatectomy specimens, we were not able to quantify nerves entering the rectum or the levator ani muscle. As a special feature, however, we quantified the nerves within the CAP. Interestingly, the ratio between periprostatic nerves and capsular nerves proved to be statistically significantly different with respect to the region of the prostate and was highest at the base (3.6) and lowest at the apex (1.9). In addition, the total number of capsular nerves increased significantly from the base (983) to the apex (2057). In conjunction with the decrease in nerve surface area from the base towards the apex, our findings support the theory that a significant number of nerves leaves the NVB on its course to innervate structures other than the corpora cavernosa. Another explanation for the decrease in total periprostatic nerve surface area from the base to the apex could be a decreasing number of ganglion cells. The presence of ganglion cells was described not only within the prostatic capsule, but also in a high percentage within the periprostatic tissue [15]. Furthermore, the presence of periprostatic ganglion cells was reported to be most frequent in the posterolateral aspect of the prostate base [16]. Ganglion cells are immunohistochemically stained and are larger than simple nerve fibres. Although we found a decrease in the number of capsular nerves from the base to the apex, we cannot answer the question as to the level of the prostate at which these nerves leave the NVB to perforate the capsule. Furthermore, it is unclear whether these nerves perforate the capsule perpendicularly or travel longitudinally in a distal direction, as do the periprostatic nerves. A shortcoming of our study is the fact that the nerves of the periprostatic tissue might be affected during prostatectomy using thermal energy sources for preparation and haemostasis (Harmonic Scalpel, diathermy). This potential influence on a study like ours could only be avoided by investigating cadaver specimens. A further shortcoming of our study is that certain anatomical regions involving a potential risk of damaging the NVB during nerve-sparing procedures; namely, the seminal vesicles and the urethroprostatic junction, could not be examined. Numerous autonomic nerve fibres surround the bladder neck, the proximal prostate, and the seminal vesicles in a cagelike fashion [10]. Some authors describe the area near the seminal vesicles as the spot where injuries to the cavernous nerves occur most frequently [10,14,17,18]. Furthermore, other authors describe a very close relation of the cavernous nerves to the lateral surface of the seminal vesicles, with distances between 3 10 mm [18]. Finally, the region of the apex and the membranous urethra bears the potential risk of damaging the NVB [1,19]. In this area, fibres of the cavernous nerves are described as being located mainly laterally and dorsally to the membranous urethra [1,10]. In our study, we were not able to investigate the nerve distribution distally to the apex. However, we were able to confirm that at the apex, the main portion of nerves is located in the dorsolateral and dorsal position, with a mean percentage of nerve surface area of 85.8%. In the dorsal position, a range of up to 45.5% was found. Our findings are in accord with those of other groups

7 359 describing a variable course of periprostatic autonomic nerves extending over the lateral and ventrolateral aspect of the prostate [2,4,10,12,18]. However, a study with more specimens would be necessary to subclassify certain types of variability of nerve distribution. Like other authors, we are unable to provide an answer to the important question of whether these nerves contribute to erectile function. Only functionalstudiesinanimalmodelsandmaleshavethe potential to clarify definitively which part of the periprostatic nerves described in anatomical studies like ours actually contributes to erectile function [20,21]. As long as the physiology of these nerves is not clearly verified by functional studies, one should undertake every effort in nerve-sparing prostatectomy procedures to preserve as many of these nerves as possible. Therefore, our results support the recommendations of other groups concerning an intrafascial nerve-sparing approach, with a high lateral incision of the periprostatic fascia in order to preserve the nerve tissue within the periprostatic fascia in the lateral and ventrolateral position [2,9,19]. This approach also became popular in the Veil of Aphrodite technique in robotic radical nerve-sparing prostatectomy [22 24]. In a study by Savera et al, this technique was investigated in terms of oncological safety and nerve preservation [25]. Savera et al studied immunohistochemically stained whole-mount sections of postprostatectomy specimens comparing histopathological features after the Veil of Aphrodite and standard nerve-sparing techniques. They clearly showed that after the standard nerve-sparing technique, a rim of lateral prostatic (periprostatic) fascia remained on the prostate in the anterolateral zone containing nerves. Veil of Aphrodite specimens lacked the lateral prostatic fascia and revealed a statistically significantly lower nerve count in this area. Furthermore, patients undergoing the Veil technique were reported to have significantly better potency outcomes than those undergoing conventional nerve-sparing [23]. However, it should be emphasized that although no strict selection criteria exist for this nerve-sparing approach to date, it should be reserved for appropriate cases so as to minimize the risk of positive surgical margins [24,26 28]. Relevant for nerve-sparing approaches are our findings that few nerves are to be found above the horizontal line at the base. On the other hand, one should consider a high percentage of dorsal nerves at the apex during the distal dissection of the membranous urethra and suturing of the urethra vesical anastomosis. 5. Conclusions The largest percentage of periprostatic nerves is located in the dorsolateral position. Periprostatic nerve distribution is variable, with a high percentage of nerves in the ventrolateral and dorsal position in some cases. The periprostatic nerve density decreases from the base towards the apex. This phenomenon is only detectable by means of computerised planimetry, not by simple quantification. A significant portion of the nerves of the NVB appears to branch into the prostate. The highest density of capsular nerves is found at the apex. Author contributions: Roman Ganzer had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Ganzer, Denzinger, Gaumann. Acquisition of data: Ganzer, Bach, Rabenalt. Analysis and interpretation of data: Ganzer, Denzinger, Blana. Drafting of the manuscript: Ganzer, Blana, Denzinger. Critical revision of the manuscript for important intellectual content: Stolzenburg, Wieland, Blana, Bach. Statistical analysis: Ganzer, Denzinger. Obtaining funding: None. Administrative, technical, or material support: Wieland. Supervision: Wieland, Stolzenburg. Other (specify): None. Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. Funding/Support and role of the sponsor: None. Acknowledgment statement: The authors would like to thank Nina Niessl for her technical support and Dr. Mathias Mueller for his excellent statistical support. References [1] Walsh PC, Donker PJ. Impotence following radical prostatectomy: insight into etiology and prevention. J Urol 1982;128: [2] Eichelberg C, Erbersdobler A, Michl U, et al. Nerve distribution along the prostatic capsule. Eur Urol 2007;51: [3] Takenaka A, Murakami G, Soga H, Han SH, Arai Y, Fujisawa M. Anatomical analysis of the neurovascular bundle supplying penile cavernous tissue to ensure a reliable nerve graft after radical prostatectomy. J Urol 2004; 172:

8 360 [4] Takenaka A, Murakami G, Matsubara A, Han SH, Fujisawa M. Variation in course of cavernous nerve with special reference to details of topographic relationships near prostatic apex: histologic study using male cadavers. Urology 2005;65: [5] Powell MS, Li R, Dai H, Sayeeduddin M, Wheeler TM, Ayala GE. Neuroanatomy of the normal prostate. Prostate 2005;65:52 7. [6] Schmid HP, McNeal JE. An abbreviated standard procedure for accurate tumor volume estimation in prostate cancer. Am J Surg Pathol 1992;16: [7] Grider MH, Chen Q, Shine HD. Semi-automated quantification of axonal densities in labeled CNS tissue. J Neurosci Methods 2006;155: [8] Ong AM, Su LM, Varkarakis I, et al. Nerve sparing radical prostatectomy: effects of hemostatic energy sources on the recovery of cavernous nerve function in a canine model. J Urol 2004;172: [9] Stolzenburg JU, Rabenalt R, Tannapfel A, Liatsikos EN. Intrafascial nerve-sparing endoscopic extraperitoneal radical prostatectomy. Urology 2006;67: [10] Lunacek A, Schwentner C, Fritsch H, Bartsch G, Strasser H. Anatomical radical retropubic prostatectomy: curtain dissection of the neurovascular bundle. BJU Int 2005;95: [11] Kiyoshima K, Yokomizo A, Yoshida T, et al. Anatomical features of periprostatic tissue and its surroundings: a histological analysis of 79 radical retropubic prostatectomy specimens. Jpn J Clin Oncol 2004;34: [12] Costello AJ, Brooks M, Cole OJ. Anatomical studies of the neurovascular bundle and cavernosal nerves. BJU Int 2004;94: [13] Lepor H, Gregerman M, Crosby R, Mostofi FK, Walsh PC. Precise localization of the autonomic nerves from the pelvic plexus to the corpora cavernosa: a detailed anatomical study of the adult male pelvis. J Urol 1985;133: [14] Baader B, Herrmann M. Topography of the pelvic autonomic nervous system and its potential impact on surgical intervention in the pelvis. Clin Anat 2003; 16: [15] Yorukoglu K, Tuna B, Kirkali Z. Ganglion cells in the human prostate. Prostate Cancer Prostatic Dis 2000; 3:34 6. [16] Sakamoto N, Hasegawa Y, Koga H, Kotoh S, Kuroiwa K, Naito S. Presence of ganglia within the prostatic capsule: ganglion involvement in prostatic cancer. Prostate 1999;40: [17] Mauroy B, Demondion X, Drizenko A, et al. The inferior hypogastric plexus (pelvic plexus): its importance in neural preservation techniques. Surg Radiol Anat 2003; 25:6 15. [18] Tewari A, Takenaka A, Mtui E, et al. The proximal neurovascular plate and the tri-zonal neural architecture around the prostate gland: importance in the athermal robotic technique of nerve-sparing prostatectomy. BJU Int 2006;98: [19] Graefen M, Walz J, Huland H. Open retropubic nervesparing radical prostatectomy. Eur Urol 2006;49: [20] Van der HC, Seif C, Boehler G, et al. Impact of electrostimulation of neurovascular bundles and pudendal nerves on the membranous urethra in male rabbits. J Urol 2006;175: [21] Tsujimura A, Miyagawa Y, Takao T, et al. Significance of electrostimulation in detecting neurovascular bundle during radical prostatectomy. Int J Urol 2006;13: [22] Menon M, Shrivastava A, Kaul S, et al. Vattikuti Institute prostatectomy: contemporary technique and analysis of results. Eur Urol 2007;51: [23] Menon M, Kaul S, Bhandari A, Shrivastava A, Tewari A, Hemal A. Potency following robotic radical prostatectomy: a questionnaire based analysis of outcomes after conventional nerve sparing and prostatic fascia sparing techniques. J Urol 2005;174: [24] Kaul S, Savera A, Badani K, Fumo M, Bhandari A, Menon M. Functional outcomes and oncological efficacy of Vattikuti Institute prostatectomy with Veil of Aphrodite nerve-sparing: an analysis of 154 consecutive patients. BJU Int 2006;97: [25] Savera AT, Kaul S, Badani K, Stark AT, Shah NL, Menon M. Robotic radical prostatectomy with the Veil of Aphrodite technique: histologic evidence of enhanced nerve sparing. Eur Urol 2006;49: [26] D Amico AV, Whittington R, Malkowicz SB, et al. The combination of preoperative prostate specific antigen and postoperative pathological findings to predict prostate specific antigen outcome in clinically localized prostate cancer. J Urol 1998;160: [27] Graefen M, Haese A, Pichlmeier U, et al. A validated strategy for side specific prediction of organ confined prostate cancer: a tool to select for nerve sparing radical prostatectomy. J Urol 2001;165: [28] Ohori M, Kattan MW, Koh H, et al. Predicting the presence and side of extracapsular extension: a nomogram for staging prostate cancer. J Urol 2004;171:

9 361 Editorial Comment on: Topographical Anatomy of Periprostatic and Capsular Nerves: Quantification and Computerised Planimetry Christian Eichelberg Urologische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, Hamburg, Germany In this excellent article by Ganzer and colleagues the authors provide further evidence, that the nerve distribution around the prostatic capsule is more complicated than previously thought [1]. Briefly, they investigated 30 prostatectomy specimens and found that 26 35% of all counted nerves are located outside the classical site for the neurovascular bundle (NVB). This is in agreement with both our previously published results [2] and additional studies described by Sievers and colleagues [3]. Collectively, these three very similar studies investigated 443 slides from 78 prostatectomy specimens and all arrive at the same conclusion; there is a high variability in prostatic nerve distribution both inter-individually as well as within a single specimen s base apex alignment. As for the NVB, the three groups found between a minimum of 46% and a maximum of 74% of all counted nerves at the position of the NVB, initially described by Lepor et al [4] (as a result of their studies on a single adult cadaver and stillborn neonates). On the other hand, the authors of the aforementioned three studies counted 15 33% of the nerves along the ventral half of the prostatic circumference (sectors 1 3) and a significant percentage (3.3 19%) was seen at the rectal aspect (sector 6), especially at the apex. While in the two recent studies nerves were visualized by immunohistochemical staining, Ganzer et al additionally performed computerised planimetry to measure the periprostatic nerve surface area [1]. However, as with the separately counted numbers of nerve fibres smaller and larger than 200 mm by Sievers et al [3], this can only offer limited new insights and indirect evidence of the real function of the outsider nerves. Where does this lead us to? Practically, it already influenced the surgical understanding since several highly respected surgeons did already recommend technical refinements for radical prostatectomy, paying tribute to these findings (refs. [5 7], among others). However, in the end the significance of extra-nvb nerves can only be proven by direct functional testing or indirectly through specific immunohistochemical staining (e.g. nitric oxide synthase). Beside this, these new findings did not change two basic principles in prostate surgery: First, even the highest incision and the longest curtain will not result in functional outcome improvements if the remaining nerve-sparing is not performed meticulously and atraumatically. Secondly, but above all, every new modification to improve functional outcome at least has to meet oncological standards previously established in terms of surgical margins and PSA relapse. References [1] Ganzer R, Blana A, Gaumann A, et al. Topographical anatomy of periprostatic and capsular nerves: quantification and computerised planimetry. Eur Urol 2008;54: [2] Eichelberg C, Erbersdobler A, Michl U, Schlomm T, Salomon G, Graefen M, et al. Nerve distribution along the prostatic capsule. Eur Urol 2007;51: (discussion 110 1). [3] Sievert K-D, Hennenlotter J, Laible I, et al. The periprostatic autonomic nerves bundle or layer? Eur Urol. In Press. doi: /j.eururo [4] Lepor H, Gregerman M, Crosby R, Mostofi FK, Walsh PC. Precise localization of the autonomic nerves from the pelvic plexus to the corpora cavernosa: a detailed anatomical study of the adult male pelvis. J Urol 1985;133: [5] Montorsi F, Salonia A, Suardi N, Gallina A, Zanni G, Briganti A, et al. Improving the preservation of the urethral sphincter and neurovascular bundles during open radical retropubic prostatectomy. Eur Urol 2005;48: [6] Graefen M, Walz J, Huland H. Open retropubic nervesparing radical prostatectomy. Eur Urol 2006;49: [7] Menon M, Shrivastava A, Kaul S, Badani KK, Fumo M, Bhandari M, et al. Vattikuti Institute prostatectomy: contemporary technique and analysis of results. Eur Urol 2007;51: (discussion 657 8). DOI: /j.eururo DOI of original article: /j.eururo