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January 2011
Endovascular Treatment of Male Varicocele
An overview of recent evidence-based literature.
Varicocele is defined as the dilatation of the veins of the pampiniform plexus. It is a well-known clinical entity that may result in mass-effect, pain, testicular atrophy, and infertility. It is estimated to be present in 40% of males with fertility issues1 and in up to 16% of male adolescents.2 The pathophysiology of varicocele is related to venous insufficiency and reflux involving the veins that drain the testis. The left internal spermatic vein (ISV) is involved more often than the right, and a bilateral presentation is seen in up to 10% of clinical varicoceles.3 Although varicocele may be first noticed as a palpable abnormality, the more important pathology associated with varicocele is that it is a known etiology for abnormal spermatic parameters leading to infertility. Fortunately, there are numerous treatment options, including endovascular, open, and laparoscopic surgical approaches.
ANATOMY AND PHYSIOPATHOLOGY
The veins of the pampiniform plexus that drain the
testis and the epididymis into the internal spermatic
vein are usually very small in diameter (up to 2 mm)
and are therefore typically difficult to visualize by ultrasound.
4 Varicoceles usually result from venous reflux in
the ISV, which may be caused by the congenital absence
of valves and/or the presence of variant collateral veins
entering the ISV and bypassing competent valves. This
abnormal venous anatomy eventually results in venous
hypertension, with enlarged and distended veins seen
along the course of the spermatic cord and epididymis.
Other causes of internal spermatic vein dilatation
and/or elevated venous pressure include extrinsic
venous compression by lymphadenopathy or other
masses and certain anatomic circumstances such as the
Nutcracker syndrome in which the left renal vein is
compressed between the aorta and the superior mesenteric
artery. Anatomic differences between the drainage
of the left and right internal spermatic veins predispose
to a higher incidence of left-sided varicoceles, because
the left ISV drains into the left renal vein, while the right drains directly into the inferior vena
cava. It has been hypothesized that
the hyperemia induced by a varicocele
produces a persistent increase in
testicular temperature, and that this
is the reason for impaired fertility
and testicular atrophy. The decrease
in testicular temperature that has
been observed in patients after varicocelectomy
treatment further suggests
that hyperthermia caused by
venous reflux into the pampiniform
plexus may contribute to the
pathology that is associated with
varicocele.5 However, there is still
controversy regarding the exact clinical
effects of a varicocele. Some
investigators have suggested that testicular
hypoxia, rather than hyperemia,
is the main mechanism leading
to male infertility and have noted
restoration of spermatogenesis after
varicocele treatment.6 Elevated
hydrostatic pressure causing a
reversed pressure gradient between
the venular and arteriolar systems in
the testicle would result in hypoxia at the level of the
seminiferous tubules.7 Therefore, by eliminating the persistently
elevated venous pressure in the testis, ligation
and/or embolotherapy are able to reverse abnormal
semen parameters (low sperm counts, decreased motility,
and abnormal sperm morphology). This has been
demonstrated in previous investigational studies.6,8,9
However, some investigators have challenged the
impact of this improvement in semen parameters upon
fertility and achieving successful pregnancy.10
CLINICAL FINDINGS AND
INDICATIONS FOR TREATMENT
The diagnosis of varicocele is made in the majority of
patients during a clinical evaluation in which the physical
examination demonstrates a palpable testicular
cord. These physical findings can be categorized as follows:
grade I (palpable only during Valsalva maneuver),
grade II (palpable in standing position), and grade III
(visible through the scrotal skin).11 Adult patients may
present with infertility, testicular atrophy, and scrotal
pain, while others may be asymptomatic. In adolescents,
asymmetry in testicular size has been used as a
criterion for intervention.12 However, normalization of
testicular volumes can occur over time, and therefore,
treatment is typically indicated only in cases in which
there is persistent or worsening
testicular asymmetry
present on an ultrasound
examination at 1-year follow-
up after diagnosis.13
Noninvasive imaging techniques
may be used to supplement the abnormal physical
examination findings in a patient in whom a varicocele
is suspected in order to confirm the diagnosis or if
there is a suspicion of malignancy. These imaging
modalities include Doppler ultrasound, computed
tomography, and magnetic resonance imaging. Doppler
ultrasound typically demonstrates numerous dilated
veins as well as increased color Doppler flow when
reflux is elicited by the Valsalva maneuver. Computed
tomography and magnetic resonance imaging are less
frequently used for varicocele evaluation unless a malignant
condition is suspected. For example, an isolated
right-sided varicocele may be more worrisome for
malignancy than if present on the left and may be further
evaluated with cross-sectional imaging.
Invasive diagnostic imaging is performed for varicocele evaluation only when there is a clinical indication for treatment. Internal spermatic venography should be performed, with initial retrograde selective catheterization of the left renal vein from either a jugular, femoral, or upper extremity transvenous approach. Contrast should be injected and images obtained with the patient performing a Valsalva maneuver and breath hold. Following left renal venography, the internal spermatic vein may be selectively catheterized and imaged with a retrograde contrast injection. Gonadal shielding and avoidance of direct gonadal radiation should be routine components of internal spermatic venography. If available, the examination may be performed on a tilted fluoroscopic table in the Trendelenburg position (Figure 1). The venographic findings may then be categorized according to either of two different currently accepted classification systems that have been described.
Bähren and colleagues14 described the anatomical findings of left-sided varicoceles based on valvular incompetence of the ISV, the presence of collateral venous channels, and anatomic variant anatomy (Table 1). This classification was subsequently used for sclerotherapy of left-sided varicoceles with the addition of subtypes demonstrating competent ISV orifice valves associated with insufficient venous collaterals bypassing the origin of the ISV.15 Duplicated gonadal (ISV) veins can also occur lower in the inguinal canal region. Murray and colleagues described this in a system, based on the location of varicocele, as renal, scrotal, and parallel duplications of the ISV. Duplications of the ISV are then subdivided into three levels: high (above the iliac crest), middle (between the iliac crest and pubic ramus), and low (below the inguinal canal).16 Although there is no evidence of any apparent correlation between the angiographic appearance of a varicocele and the clinical outcome after embolization treatment, pretreatment classification of a varicocele may be useful for procedural planning, in order to determine the best means of eliminating retrograde flow in the ISV. Moreover, venographic evaluation demonstrates the presence of collateral pathways or abnormal venous anatomy, which if unrecognized may lead to failure of either endovascular or surgical varicocele treatment.17
OVERVIEW OF ENDOVASCULAR TECHNIQUES
Since the first reports of endovascular embolization to
eliminate retrograde flow within the ISV, several techniques
have been developed. Currently, there is no universally
accepted regimen for the transcatheter endovascular
treatment of a varicocele. There have been refinements
to embolization techniques in recent years,
including the use of microcatheters and the availability
and use of various embolic materials. Several embolic
agents have been used for transcatheter embolization,
including hot contrast medium, isobutyl-2-cyanoacrylate
(glue), coils, detachable balloons, and sclerosant
agents.3,9,17-20 The choice of embolic material may reflect
operator preference, product availability in the market,
cost, ISV anatomy, and safety of use. For example, liquid/
sclerosant agents may distribute better than solid
embolic agents (eg, coils) in the presence of venous collaterals;
they can also be used alone or in combination
with solid agents. Given the heterogeneity of materials
employed for varicocele embolization, there are no
studies to date that demonstrate the superiority of any
one particular embolic agent. Furthermore, despite the
use of different embolic agents, technical success ranges
from 95% to 100% in series published in the past 10
years.3,9,17-19 Lower rates of success are mostly due to failure to catheterize the ISV. Additionally, there are several
described embolotherapy techniques, with recent
modifications tailored for the pediatric population,
allowing for preservation of the more proximal levels of
the ISV at the vessel origin. This may be important in
the event of a recurrent varicocele that might require
future intervention.18 Despite technical procedural differences,
there is consensus regarding the optimal
embolization endpoint: complete obliteration of the
ISV and venous collateral channels, starting above the
pubic symphysis or at the sacroiliac joint levels, until
reflux is no longer seen in the ISV (Figure 2).3,9,17-19
Standardization of the embolotherapy technique is evolving, particularly in the setting of duplicated gonadal veins and the presence of venous collaterals.17 High technical success rates and good clinical outcomes with retrograde sclerotherapy are well established in the literature. More recently, an antegrade approach for sclerotherapy by means of direct puncture of the plexus vein has been described in the urology literature. With antegrade sclerotherapy (Tauber procedure), a 2-cm longitudinal incision is made at the base of the scrotum in order to expose the funiculum. Subsequently, the most enlarged vein is punctured, and sclerosant material is infused under fluoroscopic guidance while a Valsalva maneuver is performed.21 This technique has been compared to the open surgical approach and has similar outcomes and complication rates.
IMPACT OF COLLATERAL VENOUS SUPPLY IN
THE VARICOCELE TREATMENT
The venous drainage of the testis is via both superficial
and deep venous systems. These two systems communicate
at the level of the cremasteric branches.
Anatomical variations at this level may result in collateral
venous drainage of a varicocele in the presence of a
normal ISV with competent valves.22 Therefore, diagnosing
the presence or absence of any abnormal venous
drainage of a varicocele has an important implication
on treatment outcomes. The incidence of venous collaterals
in the presence of a varicocele, as noted during retrograde
venography for treatment, was described to be
19% on the left and 17% on the right side.22 Undiagnosed
collateral veins are associated with treatment failures
and persistent or recurrent varicoceles.15,17,23 Moreover,
there is an increased risk of technical inability to selectively
catheterize the ISV in this setting due to the presence
of competent orificial valves in the ISV.15
Various investigators have suggested technical refinements in the evaluation and treatment of varicoceles in order to address the issues related to the presence of collateral venous channels and their potential impact upon both endovascular and surgical treatment outcomes. Collateral veins have been reported in 19% of patients undergoing laparoscopic varicocele treatment; this study further demonstrated that recognition and subsequent ligation of these vessels resulted in a very low 1% recurrence rate.22 Other investigators have recommended that the venographic evaluation of a varicocele include renal venography, with opacification of intrarenal branches in order to identify any abnormal collateral pathways or anatomical variants.23 The venogram should further delineate the entire ISV so as to identify any duplication, other collateral channels, or connecting branches (Figure 3).
One study of the endovascular treatment of recurrent postsurgical varicoceles demonstrated a high incidence of duplicated gonadal veins in the pelvic or inguinal region, leading to incomplete surgical varicocele resection/ ligation.17 In initial publications, in which retrograde sclerotherapy was used for treatment of left-sided varicoceles, recurrence rates of up to 9.8% were noted.15 In more recent series, however, recurrence rates range between 1.6% and 10%.3,19 The technical success rate of coil embolization in abnormally drained varicoceles is 73% on the left and 57% on the right. These success rates are lower than in varicoceles with normal anatomic venous drainage patterns (97%).23 These results likely reflect either additional venous collaterals that were unrecognized and untreated at the time of the procedure, or collaterals that were incompletely treated by coil embolization. Success rates ranging from 80% to 85% have been described with the use of sclerosant agents, likely as a result of the ready distribution of the agent into the collateral channels.3,15 However, the major drawback of sclerotherapy is the potential for uncontrolled sclerosant distribution into various pelvic, renal, or lumbar venous collaterals. If extensive collaterals such as these are demonstrated, embolization with a sclerosant should probably not be performed. In order to address this issue, a modified technique combining coil embolization with sclerotherapy using sodium tetradecyl sulfate has been described to obtain retrograde filling of parallel and collateral vessels. This has achieved a technical success rate of 94% in the treatment of adolescent varicoceles.18
COMPLICATIONS
Transcatheter venous embolization using a retrograde
approach is a relatively safe procedure for varicocele
treatment. Procedural complications include nontarget
embolization, vessel perforation, vasospasm, flank or
scrotal pain, phlebitis, and localized numbness. Vein
perforation may result from manipulation of guidewires and catheters through the vein valve, particularly in the
presence of competent valves and is typically self-limited.
3 Nontarget embolization can be minimized by
using occlusion balloon catheters during sclerotherapy.
Pampiniform plexus phlebitis occurs in up to 5% of
patients and is caused by passage of sclerosant material
into the peritesticular venous structures. This complication
may be avoided by external compression of the
inguinal canal during embolization. If phlebitis occurs,
treatment includes antibiotics and nonsteroidal antiinflammatory
drugs. Postembolization recurrence of
varicoceles is reported to range from 1.6% to 10% in
more recent series.3,9,19
COMPARATIVE STUDIES WITH THE
SURGICAL APPROACH
To date, there are no randomized trials in the literature
comparing endovascular and surgical techniques
for the treatment of varicocele. However, retrospective
comparative data from 1997 demonstrated that both
approaches resulted in similar rates of improvement in
semen parameters and successful pregnancy outcomes
in infertile men.24 The major advantage of transcatheter
versus surgical treatment is the absence of postprocedural
complications such as hydrocele and arterial
injury.25,26
CONCLUSION
Endovascular transcatheter embolization techniques
may be used as a minimally invasive, safe, and effective
alternative for treatment of varicocele in the adolescent
and adult population; however, to date, there are no randomized
comparative studies with surgical techniques.
The authors thank Drs. Suhny Abbara, John H. Brannen, and Florian J. Fintelmann for their assistance with this article.
Gloria M. Salazar, MD, is an assistant radiologist and instructor in radiology in the Division of Vascular Imaging & Intervention at the Massachusetts General Hospital, Harvard Medical School in Boston, Massachusetts. She has disclosed that she holds no financial interest in any product or manufacturer mentioned herein. Dr. Salazar may be reached at (617) 726-8314; gmsalazar@partners.org.
T. Gregory Walker, MD, is an associate radiologist and the Associate Director of the Fellowship in the Division of Vascular Imaging & Intervention at the Massachusetts General Hospital, and an instructor in radiology, Harvard Medical School in Boston, Massachusetts. He has disclosed that he is a paid consultant to Medtronic Endovascular, Inc., but holds no financial interest in any product or manufacturer mentioned herein. Dr. Walker may be reached at (617) 726-8314; tgwalker@partners.org.
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