CAVERNOUS
BODY REDUCTION IN FOUR PATIENTS WITH ERECTILE DYSFUNCTION DUE TO INSUFFICIENT
VENOUS OCCLUSION AND A DEFICIT OF ELASTIC FIBERS IN THE TUNICA ALBUGÍNEA
(
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FABRIZIO IACONO,
DOMENICO PREZIOSO, STEFANIA CHIERCHIA, RAFFAELE GALASSO, GENNARO IAPICCA,
MARIO DI MARTINO
Section of
Urology, School of Medicine, University of Naples “Federico II”,
Naples, Italy
ABSTRACT
Introduction:
The corpora cavernosa are cylindrical vessels containing fluid under pressure.
Thus, if cavernous wall resistance decreases, the radius increases and
internal pressure decreases (LaPlace’s law). We reasoned that if
we decrease the corpus cavernosum radius, by excising a strip from each
tunica albuginea, intracavernous pressure would increase during erection.
Materials and Methods: We treated with this
procedure, four patients (mean age 41.5) with long-standing erectile dysfunction
due to veno-occlusive dysfunction, non-responders to phosphodiesterase-5
inhibitors and intracavernous PGE1 injection.
Results: Two months post-surgery, intracavernous
PGE1 (40 mcg) induced a satisfactory erection in two patients and a 45%
and 58% tumescence in the other two. PGE1 responders also responded to
100 mg sildenafil. After 100 mg sildenafil and 20 mg tadalafil, the two
non-responders had erections that enabled penetration but were short lasting.
Conclusion: The procedure described could
be more effective than cavernous revascularization operations. The results
seem to confirm the mathematical assumptions.
Key
words: erectile dysfunction; elastic fibers; tunica albuginea;
corpora cavernosa
Int Braz J Urol. 2007; 33: 785-94
INTRODUCTION
Conservative
surgical treatment (non-prosthetic) of erectile dysfunction (ED) targets
the factors that most likely cause erectile failure and aims at restoring
physiologic conditions. Unfortunately, this goal has only partly been
achieved. For instance, the long-term outcome of corpus cavernosum microsurgical
revascularization (1), which is aimed at augmenting endocavernous pressure
during tumescence and penile rigidity, has been disappointing (2). Venous
surgery has also proven to fail in the majority of cases (3).
Because the in- (arterial) and out- (venous)
flow of blood within the corpus cavernosum is regulated by the trabecular
smooth muscles and the tunica albuginea (TA) elastic properties, revascularization
surgery will be unsuccessful if these components are damaged (4).
The severe reduction in elastic fibers in
the TA of ED subjects seems to affect TA function (5,6). Reduced TA elasticity
could reduce TA resistance when intracavernous pressure as high as during
erection (7). In fact, the corpora cavernosa are cylindrical vessels that
contain fluid under pressure. According to Laplace’s law, the larger
the vessel radius the larger the wall tension required to withstand a
given internal fluid pressure. Hence, an increase in the corpus cavernosum
radius, consequent to reduced TA elasticity, would result in a decrease
in internal pressure. Decreased TA elasticity may also reduce venous compression
so leading to veno-occlusive dysfunction (VOD) and ED. Shafik et al. proposed
a surgical technique involving the overlapping of the tunica albuginea
to reduce the volume of the cavernous cylinder with encouraging results
(8).
Here we describe a different surgical technique
for ED in patients with VOD due to a reduction in the elastic fibers of
the TA.
MATERIALS
AND METHODS
For
this treatment we selected four patients (mean age 41.5; range 24-57 y)
who had suffered from severe ED due to veno-occlusive dysfunction (VOD)
for more than 1 year, did not respond to the highest doses of phosphodiesterase-5
inhibitors nor to intracavernous PGE1 20 mcg, and refused penile prosthetic
implantation. All patients underwent medical history, IIEF, physical examination,
blood serum tests, nocturnal penile tumescence (NPT) test for three consecutive
nights, penile PGE1 Doppler flowmetry, pharmacocavernosometry. NPT test
was considered normal when at least one erection event, lasting longer
than 10 min and with a rigidity of more than 70% at the base and at the
tip, was recorded (9,10). Cavernous artery Doppler flowmetry was carried
out in basal condition and after intracavernous stimulation with PGE1
(10 mcg) (11). Pharmacocavernosometry was performed according to Goldstein
and Padma-Nathan (12).
Patients included were not smokers, nor
affected by diabetes or other endocrine diseases.
In all patients, the diagnosis of VOD was
confirmed by abnormal NPT test (Table-1), normal arterial function at
Doppler flowmetry (Table-2), dysfunctional pharmacavernosometry with absence
of erectile response at increasing intracavernous doses of PGE1 up to
60 mcg.
After rejecting penile implantation, patients
were proposed cavernous body reduction technique as a “last resource”
procedure. They were asked to sign an informed consent form and the authorization
of the Hospital Ethics Committee was obtained.
Before undergoing surgery, all patients
underwent a biopsy of the tunica albuginea with the biopsy-gun technique
(6,13,14). The TA specimens were fixed in 10% buffered formalin solution
and embedded in paraffin, and a 5-µ section was stained with hematoxylin
and eosin, and Weigert’s stain (for elastic fibers). Elastic fibers
were counted on 10 to 12 fields (40 X magnification) on five serial sections
(10 to 12 fields for each section). Routine counting techniques were used,
namely, mitotic counting, or more specifically, AgNOR counting (15). All
patients showed a severe reduction of the TA elastic fibers, i.e., between
27.77 and 49.32 for each high power field (6,13).
Eight to 10 weeks after surgery, the four
patients underwent a NPT test and a PGE1 intracavernous test with real-time
rigidometry, and then were allowed to assume PDE5 inhibitors and attempt
a sexual intercourse. Follow-up visits took place 3 and 6 months after
surgery.
Surgical
Procedure
Under general anesthesia, a subcoronal incision
is performed and the penis is skinned to the base. Buck’s fascia
is longitudinally opened with scissors along both lateral faces of the
shaft, from penis basis to balanopreputial sulcus, approximately 1 cm
dorsally to the spongy body of the urethra. The cleavage plane beneath
the fascia is bilaterally developed, circumflexes veins are ligated and
the surface of the tunica albuginea is exposed. A haemostatic tourniquet
is placed at the penis base and erection is induced through intracavernous
saline infusion. The strip to be removed from the TA, 0.5 to 1 cm wide
and just as long as the shaft is, are then marked on both faces by a demographic
pencil. The tourniquet is removed consenting detumescence and then placed
again to reduce bleeding. The TA is incised with a #11 blade along the
marked traces (Figure-1). The strips are then detached from the underlying
cavernous tissue with blunt-tipped scissors (Figure-2) and removed (Figure-3).
The TA margins are sutured by a PDS 4-0 running suture (Figure-4). Buck’s
fascia is closed through a biosyn 3-0 interrupted suture. Dartos fascia
and skin are reconstructed with biosyn 4-0 interrupted sutures.
An 18F Foley catheter is left in place for
24 hours and a compressive bandage is applied for two days. During surgery
a single bolus of antibiotics, 2 g ceftazidime, is administered. To inhibit
nocturnal erections, a 20 mg bedtime dose of diazepam is administered
in the first 7 days and an intramuscular 100 mg dose of cyproterone acetate
is administered once a week for three weeks.
RESULTS
The
postoperative course was uneventful in all patients. Two patients reported
some pain during moderate spontaneous tumescence while sleeping during
the first 20 days after surgery. The pain disappeared spontaneously.
All patients reported a relevant spontaneous
penile tumescence while sleeping or upon awaking four weeks after surgery.
Eight to ten weeks after surgery the NPT test showed a clear improvement
in all patients (Table-1) and the PGE1 (40 mcg) test with real-time rigidometry
showed: in two patients, a satisfactory erection both in rigidity (>
70%) and duration (> 10 min); in the other two patients, a rigidity
of 45% and 58% lasting 15-20 min.
At the 3 months follow-up visits the two
PGE1 responders reported good erection with sildenafil citrate 100 mg
or tadalafil 20 mg, subjectively perceived as satisfactory in terms of
both rigidity and duration. The two low-responders to intracavernous PGE1
injection had partial response to 100 mg sildenafil or 20 mg tadalafil,
reporting partial erection barely sufficient for vaginal penetration and
of insufficient duration for a satisfactory sexual intercourse.
Overall, all patients were satisfied with
the surgery. None reported functional or psychological consequences due
to the reduced penile cross-section. All declared that they did not feel
any difference and that they would undergo the operation again.
COMMENTS
During
penile erection, tumescence is caused by smooth muscle relaxation, which
exposes the lacunar spaces to systemic systolic arterial blood pressure
thus inducing blood engorgement of corpora cavernosa. As penile volume
maximizes secondary to cavernous tissue and, principally, tunica albuginea
compliance, further increment in intracavernous blood pressure will translate
into increased rigidity. Penile rigidity is then mainly influenced by
intracavernous pressure (16). However it has been shown that a wide range
of pressure can be associated with penile rigidity, and if most patients
achieve full rigidity when intracavernous pressure approaches 60-90 mmHg,
in some cased rigidity is observed at 40-50 mmHg pressure, while in some
other pressure exceeding 120 mmHg are needed. Penile geometry is considered
an important factor in explaining such variability, and it has been clearly
suggested that both length and diameter influence the intracavernous pressure
needed to achieve rigidity, and that at a given length, in presence of
a bigger diameter a higher pressure is required (17,18).
Our preliminary experience with this novel
technique seems to support a rationale for a cavernous body reduction
in patients with severe erectile dysfunction non responsive to oral or
injectable ED drugs. All four patients improved their erectile function
after the procedure, although only in two cases the response was considered
satisfactory at the post-operative real-time rigidometry. From a clinical
viewpoint, patients regained good or partial responsivity to PDE5 inhibitor
that in two cases translated in satisfactory sexual activity.
All patients were affected with VOD, and
presented good arterial function. We think these patients may prove to
be the best candidate for this procedure, although some efficacy in cases
of arteriogenic dysfunction might be shown.
Cavernous body reduction is a simple and
quick procedure, with minimal side effects. Nevertheless, it can be proposed
only to a very limited subgroup of patients, i.e. patients with severe
ED non responsive to pharmacological treatment, where a good arterial
function can be documented, who refuse penile prosthesis but not “conservative”
procedures that could possibly improve the drug-assisted erection. Patients
have also to accept a permanent reduction of penis girth, although in
our experience this can be barely perceived after the procedure.
CONCLUSION
As
penile geometry is an important factor in determining erectile function,
a tunica albuginea reduction can improve erectile function in patients
with severe ED from veno-occlusive dysfunction. This experimental procedure
can be proposed as a “last resource” technique in patients
affected with severe ED, who are bothered enough to warrant a surgical
approach but refuse penile implantation. Further experience is needed
to better define short and long-term results of this procedure, and to
identify the preoperative factors that can indicate or contraindicate
its application.
ACKNOWLEDGEMENT
Jean
Ann Gilder edited the text.
CONFLICT
OF INTEREST
None
declared.
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cavernous bodies. In: Proceedings of the First International Conference
on Cavernous Bodies Revascularization. Charles C. Thomas, Springfield,
Ill. 1980; pp. 239.
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for vascular impotence in the third millennium. J Urol. 2003; 170: 1284-6.
- Popken G, Katzenwadel A, Wetterauer U: Long-term results of dorsal
penile vein ligation for symptomatic treatment of erectile dysfunction.
Andrologia. 1999; 31 (Suppl 1): 77-82.
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TF, (ed.), World Book of Impotence. London, Smith Gordon, 1992; pp.
199.
- Goldstein AM, Meehan JP, Morrow JW, Buckley PA, Rogers FA: The fibrous
skeleton of the corpora cavernosa and its probable function in the mechanism
of erection. Br J Urol. 1985; 57: 574-8.
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disorders of tunica albuginea in patients affected by impotence. Eur
Urol. 1994; 26: 233-9.
- Bitsch M, Kromann-Andersen B, Schou J, Sjontoft E: The elasticity
and the tensile strength of tunica albuginea of the corpora cavernosa.
J Urol. 1990; 143: 642-5.
- Shafik A, Shafik I, El Sibai O, Shafik AA: Tunica albuginea overlapping:
a novel technique for the treatment of erectile dysfunction. Andrologia.
2005; 37: 180-4.
- Kessler WO: Nocturnal penile tumescence. Urol Clin North Am. 1988;
15: 81-6.
- Seoung IG, Choi HK. Reliability of Rigiscan for evaluating erectile
failure. Int J Impotence Res 1990; (suppl 1): pp 191-197.
- Barra S, Iacono F: Echo-Doppler-flowmetric assessment of penile dorsal
arteries and their role in the erectile mechanism. Eur J Radiol. 1997;
25: 67-73.
- Goldstein I, Padma-Nathan H: The interaction of arterial and venous
hemodynamics during erection: dynamic infusion cavernosometry and cavernosography.
AUA, New England Sect 1987; pp. 18 (abstract).
- Iacono F, Barra S, De Rosa G, Boscaino A, Lotti T: Microstructural
disorders of tunica albuginea in patients affected by Peyronie’s
disease with or without erection dysfunction. J Urol. 1993; 150: 1806-9.
- Wespes E, Depierreux M, Schulman CC: Use of bBiopty gun for corpus
cavernosum biopsies. Eur Urol. 1990; 18: 81-3.
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et al.: Nucleolar organizer regions in aggressive and nonaggressive
basal cell carcinoma of the skin. Cancer. 1992; 69: 123-6.
- Lavoisier P, Proulx J, Courtois F: Reflex contractions of the ischiocavernosus
muscles following electrical and pressure stimulations. J Urol. 1988;
139: 396-9.
- Desai KM, Floyd TJ, Follett DH, Peake DR, Gingell JC: Development
of a penile rigidity indicator and new concepts in the quantification
of rigidity. Br J Urol. 1988; 61: 254-60.
- Puech-Leao P, Akira S, Chao S: Penile architecture and intracavernous
pressure: a simulation. Int J Impot Res. 1997; 4 (suppl 2), 43.
____________________
Accepted after revision:
June 26, 2007
_______________________
Correspondence address:
Dr. Fabrizio Iacono
Via Tasso 480, 80127
Naples, Italy
Fax: + 3 908 1060-9149
E-mail: fiacon@tin.it
EDITORIAL COMMENT
The
authors report an interesting experience with a new surgical technique
(cavernous body reduction) in 4 patients suffering from severe erectile
dysfunction (ED) non-responsive to oral or injectable ED drugs. In all
the patients the diagnosis of veno-occlusive dysfunction (VOD) was confirmed
by abnormal nocturnal penile tumescence (NPT) test, dynamic Doppler flowmetry,
blood examination and pharmaco-cavernosometry.
Before
undergoing surgery, all patients underwent a biopsy of tunica albuginea
(TA) with the biopsy-gun technique; the TA specimens showed a severe reduction
of TA elastic system fibers.
The
technique described by the authors is inspired by Shafik’s work.
Shafik et al. proposed a surgical technique involving the overlapping
of TA to reduce the cavernous cylinder volume with encouraging results.
The aim of this work is to highlight the role of TA in the erectile mechanism;
in fact, we agree that TA is not a pure holder of corpora cavernosa, but
its integrity is crucial for the physiology of erection.
We
just propose some considerations about patients’ inclusion criteria.
The diagnosis of veno-occlusive dysfunction in patients affected by ED
without any other possible cause is moreover a big challenge for andrologists:
- The selected
patients have suffered from ED for more than 1 year, but it is not clear
if the sexual dysfunction is an acquired or a congenital disease; in
fact, the onset of severe acquired ED due to reduction of elastic fibers
could be related to other systemic or metabolic affections. Have endocrine
blood examinations been performed? As well as an important step in the
management of andrological patient, an androgen deficiency, also partial,
could be responsible for a diminished trophism in many organs, including
TA.
- The relationship
between reduction of TA elasticity, TA resistance and the corpus cavernosum
radius it is not clear. TA elasticity, as we believe, is a crucial point
to induce detumescence with a ten fold increase of its thickness.
- The Authors
do not report any consideration about psychological assessment concerning
sexological aspects. We believe that this evaluation has a precise role
in order to identify patients with high levels of anxiety or depression.
In fact it is well known that these conditions determines a series of
biochemical changes in brain and body; particularly sympathetic hyperactivity
with increased blood levels of catecholamines induces vasoconstriction
and increased penile smooth muscle tone. In these patients pharmaco-cavernosometry
can give false results. Moreover, these patients are frequently affected
by sleep disorders. It would have been interesting to perform a nocturnal
polysomnogram test that, together with nocturnal penile tumescence test,
could lead to a more certain diagnosis.
The
surgical technique is mainly based on a volumetric reduction of corpora
cavernosa and implies an irreversible alteration of penile anatomy.
Our major objections to the authors are the following:
- Follow
up is too short to obtain certain results (moreover they are not successful
as reported by the authors themselves); in fact a partial and brief
success of the technique could be related to ligation of circumflexes
veins (as reported in literature).
- At that
moment the patients did not accept penile prosthesis implant; but were
they informed that cavernous body reduction could compromise, in the
future, this kind of surgery?
In
conclusion, this article is really interesting for an innovative approach
to ED patients non-responders to oral or injectable drugs. But a short
follow up may have biased the findings of the authors. It would be interesting
to be informed about the future clinical condition of these patients.
Dr. Marco Grasso
Department of Urology, Desio Hospital
San Raffaele Hospital, Milan
E-mail: marco.grasso@aovimercate.org
EDITORIAL COMMENT
The
article “Cavernous Body Reduction in Four Patients with Erectile
Dysfunction Due To Insufficient Venous Occlusion and a Deficit of Elastic
Fibers in the Tunica Albuginea” is very similar to the published
article “Shafik A, Shafik I, El Sibai O, Shafik AA: Tunica albuginea
overlapping: a novel technique for the treatment of erectile dysfunction.
Andrologia. 2005; 37: 180-184”. This technique in our study was
applied on nine patients instead of four patients in this study; we assumed
that authors would increase the number of patients in order to provide
the readers with better statistical analysis or to prolong the follow
up period for more evaluation of the outcome. The title is deceiving,
in which it appears as a new technique. The aim of work is not clear weather
to our technique [according to Shafik technique] or to compare with other
techniques. The discussion is poor in comparison to our article on 2005.
In fact, our novel technique is based on histopathologic study demonstrating
the pathogenesis of tunica albuginea in venogenic erectile dysfunction
patients, in which the technique is dealing with the pathology. Since
our aforementioned article we reached 24 patients underwent that technique
and we are about to publish the results.
Dr.
Ali A. Shafik
Associate Professor of Surgery
Cairo University
Cairo, Egypt
E-mail: shafik@ahmedshafik.com
REPLY BY THE AUTHORS
We
presented our surgical technique for the first time at the National Congress
of the Italian Society of Urologists in June 2004 and reported the initial
data (1). The Shafik et al. publication came out a year later. Shafik’s
surgical technique, although part of a similar rationale and one, therefore,
that supports our theories which have already been published on several
occasions, involves overlapping of the albuginea rather than the removal
of a piece of tissue. Overlapping, in our opinion, leads to thickening
of the corpus cavernosum and reduced longitudinal expansion of the penis
during erection.
The
four patients operated on all suffered from erectile deficit of organic
origin as was revealed by the diagnostic tests carried out and by the
lack of response to the vasoactive drugs administered. No psychological
assessment would have altered the diagnosis and so it was not considered
appropriate to carry out psychological tests. There may have been a psychological
component overlaying the obvious organic etiology but this would not have
affected the therapy in any way. The endocrine blood examination of all
patients was performed. No endocrine or metabolic disease was identified.
We
were the first to demonstrate (2-5) and then other authors did the same
(6,7) that patients presenting with erectile dysfunction (ED) are affected
by a damaged tunica albuginea (TA) with reduced elastic fibers. Numerous
authors have demonstrated the function of the elastic fibers in the microstructure
of the tunica albuginea. It appears that a reduction in the elastic fibers
in the tunica albuginea of the corpus cavernosum affects the veno-occlusive
function of the tunica. Why patients with ED have reduced elastic fibers
is not yet known. It may be that it is an acquired syndrome, but we do
not know.
Our
own experience, based on dozens of surgical operations carried out by
our team to try and solve cases of veno-occlusive dysfunction ED, involving
massive ligature of the venous cavernous area, including stripping of
the penal dorsal vein, and ligature of the crural and all circumflex veins,
has shown that results are very disappointing even one month post surgery.
What is more, results published by numerous other authors demonstrate
the failure of these surgical procedures both in the short as well as
in the long term (8-11). It is our opinion that simple ligature of a vein
in the corpus cavernosum cannot (unfortunately) improve erectile function
in any way.
Normally
the arterial blood flow reaching the two corpora cavernosa through the
right and left cavernous arteries corresponds to the amount of venous
blood flowing back from the cavernous circulation leaving the penis through
the triple venous system.
One
of the main vascular mechanisms, which can determine the pressure increase
inside the penis and, lastly, the erection, is the trans-albugineal veins
compression. These veins are compressed by the TA while the corpora cavernosa
fill in, resulting in a strong reduction of the blood drainage from the
corpora cavernosa. The penis fills in as a consequence of the flow rate
increase, since the excitement phase leads to an increase in both the
vessel diameter and the systolic rate.
The
flow rate is expressed by the following formula Q = A*v [1] where ‘A’
is the vessel cross-section and ‘v’ is the mean rate. Since
v = DP*r2/8nl [2] where ‘n’ is the blood viscosity, the replacement
of [1] with [2] yields Q = DP 3.14 r4/8nl (2 a) which clearly helps to
understand that even a slight vessel ray increase could dramatically augment
the flow rate.
The
progressive pressure increase inside the corpora cavernosa compresses
the trans-TA venules, reducing the flow rate and generating an imbalance
between the Qi (in- flow rate) and the Qu (out- flow rate). Therefore
Qi >> Qu.
Under
normal conditions La Place’s law explains the tension generated
on the corpora cavernosa wall structure, i.e. on the TA, assuming that
the two corpora cavernosa can be considered as infinitely long cylinders,
so r2 = ∞, also deducing that p = t / r1 or also that t = p * r1.
There
is an important consequence of this law: in order to reach an established
pressure inside a container, a higher tension is required if the curvature
ray is higher.
It
is then clear enough how fundamental the role played by the TA is in the
erectile phenomenon. The baseline TA structure is made up of wavy looping
collagen bands, and of elastic fibers bridging the loops while providing
elasticity to the collagen structure. During the erectile event, the loops
would be changed only slightly in their fundamental structure. Nonetheless,
there is still an increase in the corpus cavernosum diameter, which is
regulated by Young’s module, where we notice: DR = P*r2 / 2 E*s
* (2-v) [3] where ‘E’ is the elasticity coefficient and ‘v’
is Poisson’s coefficient.
Thanks
to this law, it is clear that, if pressure remains stable, a cylinder
wall elasticity decrease corresponds to a cylinder curvature ray increase.
By this formula, P can be obtained, P = 2 E* s * Dr / r2 * (2-v) [4].
It is remarkable that a minimal cylinder ray increase results in a substantial
reduction of the inner cylinder pressure. It is obvious that the higher
the study material elasticity, the higher the structure inner pressure.
A reduction of the elastic fibers inside the TA would cause a change in
the normal collagen loops structure: their flattening would result in
a longer period, an overall increase in the cylinder structure ray and
a subsequent pressure drop by stable flow (erectile failure).
The
authors do not believe that the cavernous body reduction could compromise
future penile prosthesis implant.
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