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Recovery of sexual function after nerve-sparing radical retropubic prostatectomy: is cavernous nitric oxide level a prognostic index?

Abstract

The preservation of NANC nerve fibers (producing nitric oxide, NO) is necessary for erection recovery after retropubic radical prostatectomy (RRP). Yet, it is impossible to establish when and if a patient will recover erections; therefore, we investigate the prognostic value of cavernous blood NO levels on this parameter. Nerve-sparing RRP was performed on 14 patients for localized prostate cancer. We evaluated all patients 3 months after surgery by IIEF score: no patients had erections. A cavernous blood sample was also taken to determine NO levels (as nitrite). Patients were evaluated again 18 months after surgery. In six cases, erectile function was compromised, whereas in seven cases, potency was restored. Statistical analysis showed a relationship between nitrite levels in cavernous blood 3 months after surgery and the recovery or erectile function at 18 months. We propose that cavernous NO blood levels are a prognostic index of erection recovery.

Introduction

Erectile dysfunction often follows radical retropubic prostatectomy (RRP). Previous studies have shown that the recovery of erectile function occurs in 41–69% of subjects in a period ranging from 6 to 18 months, provided that at least one of the neurovascular bundles is preserved.1, 2, 3

Data in the experimental animal have shown that the improvement and the recovery of erectile function is probably due to the regeneration of nerve fibres, particularly those producing nitric oxide (NANC fibres).4, 5, 6 The interruption of NANC fibres, during radical prostatectomy, leads to permanent erectile dysfunction, whereas the preservation of at least one neurovascular bundle permits nerve regeneration and the spontaneous recovery of erectile activity within 6–18 months.4

Nitric oxide (NO) is one of the most important mediators of the complex mechanism involved in erection and it is formed by NO synthase (NOS).7, 8, 9, 10, 11 Three different NOS isoforms (I, II, III) occur in human tissues.5 In bilateral neurological damage, isoform I decreases and isoforms II and III alone are not able to produce the NO levels necessary for achieving erection, unless the nerve pathway is also intact. For this reason, it is extremely important to preserve, at least partially, the neurovascular bundles during surgery not only to ensure proper NOS levels but also, above all, to promote regeneration of the fibres producing NO.

In most patients, it is not possible to establish previously if and when erectile function will be recovered after NS-RRP. Therefore, the aim of our study is to correlate the spontaneous recovery of erectile function 18 months after surgery and cavernous blood NO (nitrite) levels 3 months after surgery, as prognostic value after NS-RRP.

Patients and methods

Patients

From January 2002 to January 2003, we performed monolateral or bilateral nerve-sparing RRPs on 14 patients with a mean age of 61 years (range 55–68 years) affected by clinically localized prostate cancer (T1–T2). All patients were evaluated preoperatively from a sexual standpoint, performing a detailed sexual evaluation and using the IIEF questionnaire12 (Question nos. 1–5 and 15).

At 3 months after surgery, the patients were evaluated again by IIEF. During erection induced by prostaglandin intracavernous injection (10 μg of PGE1; Caverject, Pfizer, New York, USA), a blood sample was drawn from the corpus cavernosum to examine nitrite content. All patients were re-evaluated 18 months postoperatively by IIEF and sexual evaluation.

NO determination

NO is a short-lived radical and spontaneously produces nitrite. For this reason, NO is evaluated as nitrite in the present study.

Plasma was obtained from heparinated blood samples. Aliquots (20–50 μl) of plasma were used for the electrochemical determination of nitrite as described previously.13

Statistical analysis

Nonparametric test of Mann–Whitney for unpaired data, and Spearman rank correlation coefficient (rho) were performed using SPSS for Windows release 10.0.1 (SPSS Inc., Chicago, IL, USA, 1999). The significance level was set at P<0.05.

Results

Evaluation of patients by IIEF score

All patients showed potency at the preoperative examination, with an average IIEF score12 (Question nos. 1–5 and 15; possible score 0–30) of 27.5.

At the first postoperative follow-up, after 3 months, none of the patients showed spontaneous erections but only tumescence; none of them could have sexual intercourses.

Only 13 patients could be evaluated 18 months after surgery, because one of them had a relapse of the disease. Six patients (40%) presented severe to moderate erectile dysfunction (median IIEF score 6; range 0–13), whereas in seven cases, sexual potency was either entirely or partially restored and patients could have sexual intercourses (median IIEF score 26; range 17–30).

Evaluation of cavernous nitrite 3 months after surgery

Patients could be divided as to their corporal nitrite concentration, into two groups. The median NO (nitrite) of one group was 71 nmol/l (range 30–188 nmol/l), whereas in the other group, it was 608 nmol/l (range 328–800 nmol/l) (Figure 1).

Figure 1
figure1

Relationship between nitrite concentration in carvernous blood samples (3 months after surgery) and IIEF scores (18 months after surgery). Spearman's rho 0.085; P<0.0001.

Relationship between IIEF score 18 months after surgery and the cavernous nitrite 3 months after surgery

Statistical analysis showed a close relationship between the degree of erectile function recovery 18 months after surgery and cavernous nitrite levels (rho=0.805; P<0.001), as reported in Figure 1.

Finally, the patient with biochemical relapse of the disease experienced erections before the treatment with androgenic blockage (8 months after surgery). His nitrite levels exceeded 500 nmol/l.

Discussion

RRP procedure is burdened by two main complications: incontinence and erectile dysfunction. Although many technical modifications have been proposed to achieve a good continence rate (over 95%), this has not occurred for erectile dysfunction.

At the moment, there are no diagnostic or instrumental methods able to predict whether or not a patient will recover erectile function after surgery; in our case study, seven patients (57%) recovered erectile function, but six (43%) did not.

We determine NO as nitrite, formed by reaction of NO with oxygen.14 Nitrite is the major final product of NO metabolism and mirrors the cellular production of NO.15

Since our patients had no spontaneous erections 3 months after surgery, we could not use video movies to induce sexual excitement, as previously done by others,16 who found no correlation between erection and NO concentration in cavernous blood. Since erection is a multifactorial phenomenon, the different way of inducing it may justify different results. Moreover, we use surgical patients here and not normal volunteers.

The data presented here indicate that nitrite levels, determined 3 months after surgery in cavernous blood, were lower in the group of patients who did not later recover erectile function. On the contrary, high nitrite values were observed in the patients recovering erectile function 18 months after surgery.

Therefore, cavernous nitrite levels are proposed as a prognostic factor for patients undergoing radical prostatectomy: low nitrite levels could indicate a difficult or unlikely recovery of erectile function, whereas high levels could indicate a good probability of recovery.

Conclusions

Our data suggest that the evaluation of corporal blood nitrite 3 months after surgery can be proposed a prognostic test for the evaluation of penile erection recovery in RRP operated patients.

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Correspondence to G Arienti.

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Zucchi, A., Arienti, G., Mearini, L. et al. Recovery of sexual function after nerve-sparing radical retropubic prostatectomy: is cavernous nitric oxide level a prognostic index?. Int J Impot Res 18, 198–200 (2006). https://doi.org/10.1038/sj.ijir.3901392

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Keywords

  • erectile dysfunction
  • nerve-sparing radical retropubic prostatectomy
  • nitric oxide

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