Surgical Skills Course November 2006

NERVE ADVANCEMENT WITH END-TO-END RECONSTRUCTION DURING ROBOTIC RADICAL PROSTATECTOMY: TRYING TO IMPROVE SEXUAL OUTCOMES IN PATIENTS WITH EXTRACAPSULAR EXTENSION

Erectile dysfunction remains a common problem after radical prostatectomy when one or both neurobundles were resected. Radical Prostatectomy is considered nowadays the standard treatment for localized prostate cancer.

Since the introduction of the nerve sparing technique by Walsh, several series have been published in which patients recover their erectile function. Worse results were reported in previous series featuring cases where non-sparing techniques were applied. Therefore, it is clear that some patients require a total or partial, bilateral or unilateral, neurovascular bundle resection for oncological safety to be guaranteed. Kim and Scardino reported use of sural nerve as a graft to preserve erectile function. According to their outcome 1 year after surgery, intercourse was possible in only 33% of patients.

We proposed an absolutely new approach for these patients using Robotic Skills. Based on 3-dimensional visualization with magnification, technical advantages for intracorporeal suturing and knot tying, precise Neurovascular Bundle (NVB) dissection and better surgical dexterity that Da Vinci System provides, it’s feasible to do a primary anastomosis of the both ends of NB with a previous mobilization “Nerve Advancement Technique (NVBA)” of them. As well we describe the new concept of “Incremental Nerve Sparing (INS)” that will be explain subsequently.

The feasibility of end-to-end nerve and end-to-side suture resulting in nerve regeneration was proved a long time ago. To the best our knowledge, this is the first description of this technique in order to restore continuity of cavernous nerves, which are resected during robotic radical prostatectomy. In January 2005 we performed the first case, and till today, we already completed a total of 10 cases. We described in this paper our initials results of patients with more than 14 months of follow-up.

TECHNIQUE DESCRIPTION
Robotic Radical Prostatectomy (RRP)
Port placement and all the step of RRP was performed using the main operative steps described previously. The procedure includes bilateral pelvic node dissection.

Release of NVBs and Incremental Nerve Sparing
The prostate is retracted on one side and the lateral pelvic fascia is exposed. The layers of the periprostatic fascia fuse with the anterior layer of Denonvillier’s fascia lateral to the prostate to form a potential triangular space containing the NVBs. The inner layer of the periprostatic fascia forms the medial vertical wall of this triangle; the outer layer or the lateral pelvic fascia forms the lateral wall and the anterior layer of the Denonvillier’s fascia forms the posterior wall. Entering the triangular space between Denonvillier’s fascia posteriorly, lateral pelvic fascia laterally and the prostate medially best preserves the nerves. The surgeon has to reflect the lateral pelvic fascia off the prostate. It is incised in a plane superficial to the prostatic fascia from apex to prostato-vesical junction, always staying parallel to the NVBs. It is then swept off the prostate using gentle sweeping movements. This maneuver releases the bundles and provides landmarks for later antegrade dissection. Dissection is totally athermal with clips preferred for any vascular control. This dissection is continued distally to the apex and both posteriorly and laterally. Further dissection proceeds within the triangle to release the bundles staying close to the prostatic fascia. Near the apex a few perforators are clipped and transected allowing the NVB to fall away from the apex. After unilateral or bilateral bundle resection, both ends are released from the laterorectal area.

Figure 1

Figure 2

End-to-End Anastomosis
Using two robotic needle drivers and a 6-zero polypropylene suture, we performed a two or three an interrupted suture between both stumps without tension.

Figure 3

Figure 4

RESULTS and DISCUSSION
During 2005 we performed in 7 potent men (Mean Age and Mean SHIM Score) with clinically localized prostate cancer underwent RRP in a single institution by a single surgeon (AT). All were strongly motivated to maintain sexual function. Our decision to perform a partial excision of one of the bundles was based on the intraoperative findings (including results of frozen sections) as well as on preoperative data (palpable cancer, high volume disease, high Gleason Score). In this study we also introduce our new concept of “Incremental Nerve-Sparing”. This technique is based on the minimal resection of the NVBs. We do this in order to excise the entire tumour but attempt to keep as much of the bundle as possible. All the patients signed an institutional review informed consent where all the details of the procedure were clarified.

We performed unilateral partial resection (“Incremental Nerve-Sparing”), nerve-end advancement and finally end-to-end anastomosis in six patients while in one patient we did a bilateral parcial excision, nerve-end advancement and bilateral end-to-end anastomosis.

Sexual function preservation after RRP without compromising oncological results remains an important goal. Reported potency results after RRP vary widely from 20% to 97% at 12 months.
Extracapsular extension (ECE) of cancer is found in about 40% of Radical Prostatectomy specimens. Positive surgical margins (PSM) are disturbingly common in 2% to 59% of RRP specimens.
It’s still difficult to determine which patients will have ECE of cancer in the NB area. Several strategies have been implemented to try and predict whether a tumour is organ confined or extracapsular, based on digital rectal examinations, the Gleason score in the preoperative biopsy, MRI and ultrasonography or intraoperative findings such as open palpation results or endoscopic landmarks, but although useful, none of them has proved to be a hundred percent reliable or accurate.

In advanced cancers uni or bilateral NVB excision should be considered when a substantial risk of ECE exist in the area of NB. However, it has been proved that total resection of both NVB results in patients losing spontaneous erection adequate for intercourse. In this respect, Kim and Scardino suggested in 1999 sural nerve grafting to replace the resected cavernous nerves after radical prostatectomy. After a one and two years of follow-up, overall erectile activity return in 9 of 12 patients (75%) and then in 16 of 23 patients (69%)
Turk first replicated this technique in laparoscopic surgery and then robotically by Kaouk, both with very initial results.
Thus, it’s appears that the long-term results of sural nerve graft replacement of cavernous nerves awaits final validation.

We are proposing a new approach to the treatment of these patients, based on the following:

1. The magnified optics (10-fold) and 3-dimensional visualization that RRP provides (combined with intraoperative surgical landmarks identification) might enable a less aggressive bundle resection (Incremental Nerve-Sparing), thus diminishing the end-to-end gap. Frozen biopsies might be used as an additional helpful tool to determine the non-existence of positive margins before anastomosis.

2. Precise dissection of NVB from the prostate and surrounding tissue is facilitated by the use of the robot. This in turn facilitates nerve-end advancement in order to further decrease the gap between nerve stumps and enable a tension-free end-to-end anastomosis.

3. The three-dimensional magnification enhances dexterity and eliminates tremors, and enables precise suturing and approximation of the NVB stumps (perineural sheath are inside) in microsurgical anastomoses.

The basic neuroscientific concept underlying the possibility of reparing a peripheral nerve is well known since a long time. According to Geuna et al.,if continuity is re-established between proximal and distal nerves stumps by end-to-end suture, the axons arising from the rich terminal sprouting occurring immediately upstream to the point of transection will rapidly grow along the glial colums in distal nerve stumps (bands of Büngner) and eventually reinervate the denervated territories.

Over the last 15 years other concept of nerve repair has risen, end-to-side neurorraphy. Obtaining nerve fibber regeneration along the distal stump of a transacted nerve by inducing collateral axonal sprouting from a neighbour healthy donor nerve.

In our initial series, only one patients (14%) presented positive surgical margin on the specimen considering that 85% of them were classified as pT3 disease. In terms of sexual function, of our previously potent men (IIEF>18), a 66% of them recovered functional erections after surgery with a median follow-up period of 12 months. 

Finally, the procedure is technically feasible, oncologically safe and the results on sexual function are very promising. However, further experience and longer follow-up are necessary to validate the results of this pilot study.

References
1.Scardino PT, Kim ED. Rationale for and results of nerve grafting during radical prostatectomy. Urology 2001;57:1016-9.
2.Geary ES, Dendinger TE, Freiha FS, Stamey TA. Nerve sparing radical prostatectomy: a different view. J Urol 1995;154:145-9.
3.Quinlan DM, Epstein JI, Carter BS, Walsh PC. Sexual function following radical prostatectomy: influence of preservation of neurovascular bundles. J Urol 1991;145:998-1002.
4.Rabbani F, Stapleton AM, Kattan MW, Wheeler TM, Scardino PT. Factors predicting recovery of erections after radical prostatectomy. J Urol 2000;164:1929-34.
5.Catalona WJ, Bigg SW. Nerve-sparing radical prostatectomy: evaluation of results after 250 patients. J Urol 1990;143:538-43.
6.Kim ED, Nath R, Kadmon D, Lipshultz LI, Miles BJ, Slawin KM, Tang HY, Wheeler T, Scardino PT. Bilateral nerve graft during radical retropubic prostatectomy: 1-year followup. J Urol 2001;165:1950-6.
7.Kim ED, Nath R, Slawin KM, Kadmon D, Miles BJ, Scardino PT. Bilateral nerve grafting during radical retropubic prostatectomy: extended follow-up. Urology 2001;58:983-7.
8.Kim ED, Scardino PT, Hampel O, Mills NL, Wheeler TM, Nath RK. Interposition of sural nerve restores function of cavernous nerves resected during radical prostatectomy. J Urol 1999;161:188-92.
9.Kim ED, Scardino PT, Kadmon D, Slawin K, Nath RK. Interposition sural nerve grafting during radical retropubic prostatectomy. Urology 2001;57:211-6.
10.Binder J, Kramer W. Robotically-assisted laparoscopic radical prostatectomy. BJU Int 2001;87:408-10.
11.Geuna S, Papalia I, Tos P. End-to-side (terminolateral) nerve regeneration: a challenge for neuroscientists coming from an intriguing nerve repair concept. Brain Res Brain Res Rev 2006;52:381-8.
12.Walsh PC, Donker PJ. Impotence following radical prostatectomy: insight into etiology and prevention. J Urol 1982;128:492-7.
13.Walsh PC. Anatomic radical prostatectomy: evolution of the surgical technique. J Urol 1998;160:2418-24.
14.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;172:1032-5.
15.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;65:136-42.
16.Tewari A, Peabody JO, Fischer M, Sarle R, Vallancien G, Delmas V, Hassan M, Bansal A, Hemal AK, Guillonneau B, Menon M. An operative and anatomic study to help in nerve sparing during laparoscopic and robotic radical prostatectomy. Eur Urol 2003;43:444-54.
17.Tewari A, El-Hakim A, Horninger W, Peschel R, Coll D, Bartsch G. Nerve-sparing during robotic radical prostatectomy: use of computer modeling and anatomic data to establish critical steps and maneuvers. Curr Urol Rep 2005;6:126-8.
18.Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Pena BM. Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res 1999;11:319-26.
19.Ficarra V, Cavalleri S, Novara G, Aragona M, Artibani W. Evidence from Robot-Assisted Laparoscopic Radical Prostatectomy: A Systematic Review. Eur Urol 2006, in press.
20.Wieder JA, Soloway MS. Incidence, etiology, location, prevention and treatment of positive surgical margins after radical prostatectomy for prostate cancer. J Urol 1998;160:299-315.
21.Graefen M, Haese A, Pichlmeier U, Hammerer PG, Noldus J, Butz K, Erbersdobler A, Henke RP, Michl U, Fernandez S, Huland H. A validated strategy for side specific prediction of organ confined prostate cancer: a tool to select for nerve sparing radical prostatectomy. J Urol 2001;165:857-63.
22.Turk IA, Deger S, Morgan WR, Davis JW, Schellhammer PF, Loening SA. Sural nerve graft during laparoscopic radical prostatectomy. Initial experience. Urol Oncol 2002;7:191-4.
23.Kaouk JH, Desai MM, Abreu SC, Papay F, Gill IS. Robotic assisted laparoscopic sural nerve grafting during radical prostatectomy: initial experience. J Urol 2003;170:909-12.
24.Terzis JK, Sun DD, Thanos PK. Historical and basic science review: past, present, and future of nerve repair. J Reconstr Microsurg 1997;13:215-25.
25.Hall S. The response to injury in the peripheral nervous system. J Bone Joint Surg Br 2005;87:1309-19.

QUESTIONS

Question 1
Which was, under Kim & Scardino technique, proposed in 1999, the nerve used as graft?

1. Genitofemoral
2. Abdomino-Cutaneo
3. Obturator
4. Sural

Correct answer: D
Kim and Scardino suggested in 1999 sural nerve grafting to replace the resected cavernous nerves after radical prostatectomy.

Question 2
What “Incremental Nerve-Sparing” technique does it mean?

1. This technique is based on the minimal resection of the NVBs
2. Complete Neurovascular resection
3. Intrafascial Approach
4. Extrafascial Approach

Correct answer: A
In this study we also introduce our new concept of “Incremental Nerve-Sparing”. This technique is based on the minimal resection of the NVBs. We do this in order to excise the entire tumour but attempt to keep as much of the bundle as possible.

Question 3
Name main “Nerve-Advancement” technique advantage.

1. To avoid inserting a heterotopic tissue between bundle two ends.
2. To minimize resection, keeping as many as possible nerve terminals.
3. To make possible a territory reinervation by means of nerves regeneration.
4. All previous answers.

Correct answer: D
The basic neuroscientific concept underlying the possibility of repairing a peripheral nerve is well known since a long time. According to Geuna et al, if continuity is re-established between proximal and distal nerves stumps by end-to-end suture, the axons arising from the rich terminal sprouting occurring immediately upstream to the point of transection will rapidly grow along the glial columns in distal nerve stumps (bands of Büngner) and eventually reinervate the denervated territories.

Over the last 15 years other concept of nerve repair has risen, end-to-side neurorraphy. Obtaining nerve fibber regeneration along the distal stump of a transacted nerve by inducing collateral axonal sprouting from a neighbour healthy donor nerve.

Question 4
How long you have to wait to evaluate results in a patient with nerve graft?

1. 6 weeks
2. 18 months
3. 6 months
4. 12 months

Correct answer: B
See the following references:

Kim ED, Nath R, Kadmon D, Lipshultz LI, Miles BJ, Slawin KM, Tang HY, Wheeler T, Scardino PT. Bilateral nerve graft during radical retropubic prostatectomy: 1-year followup. J Urol 2001;165:1950-6.

Kim ED, Nath R, Slawin KM, Kadmon D, Miles BJ, Scardino PT. Bilateral nerve grafting during radical retropubic prostatectomy: extended follow-up. Urology 2001;58:983-7.

Kim ED, Scardino PT, Hampel O, Mills NL, Wheeler TM, Nath RK. Interposition of sural nerve restores function of cavernous nerves resected during radical prostatectomy. J Urol 1999;161:188-92.

Kim ED, Scardino PT, Kadmon D, Slawin K, Nath RK. Interposition sural nerve grafting during radical retropubic prostatectomy. Urology 2001;57:211-6.

Question 5
Who are the ideal candidates that could benefit from this new technique?

1. Patients with a preoperative SHIM minor to 12
2. Patients with a preoperative SHIM greater than 18 and a T3 clinical stage
3. Patients with Gleason 7 (4+3)
4. Any type of patients

Correct answer: B
In our initial series, only one patients (14%) presented positive surgical margin on the specimen considering that 85% of them were classified as pT3 disease. In terms of sexual function, of our previously potent men (IIEF>18), a 66% of them recovered functional erections after surgery with a median follow-up period of 12 months. 

Finally, the procedure is technically feasible, oncologically safe and the results on sexual function are very promising. However, further experience and longer follow-up are necessary to validate the results of this pilot study.