A Randomized Trial Comparing 2 Doses of Polidocanol

Sclerotherapy for Hydrocele or Spermatocele

Staffan Jahnson,* Dag Sandblom and Sten HolmängFrom the Department of Urology, Institution of Clinical and Experimental Medicine, Linköping University, Linköping (SJ), Örebro UniversityHospital, Örebro (DS), and Sahlgrenska University Hospital, Göteborg (SH), Sweden

Purpose: Polidocanol sclerotherapy for hydrocele or spermatocele combines highefficiency with low morbidity, but the optimal dose is not known. We comparedthe efficacy and morbidity of 2 or 4 ml polidocanol sclerotherapy for hydrocele orspermatocele.Materials and Methods: From 1993 to 2005 a double-blind randomized clinicaltrial was conducted using 2 or 4 ml polidocanol (30 mg/ml) for sclerotherapy ofhydrocele/spermatocele in 224 evaluable patients at 3 university hospitals. Fluidwas evacuated and 2 or 4 ml polidocanol was administered by a nurse, with theamount injected concealed from others present. At 3-month followup morbiditywas ascertained using a questionnaire completed by the patients. Fluid recur-rence was determined clinically and generally re-treated.Results: After the first treatment, cure was observed in 59% and 47% in the 4and the 2 ml group, respectively (p � 0.04). More patients in the 4 ml group hadcomplications (31% vs 18%, p � 0.04). Complications were mostly of low ormoderate intensity and seldom required medication. After 1 to 4 treatments 200of 224 patients (89%) were cured and another 10 (5%) had small amounts ofresidual fluid, with no difference between the groups. Of the patients withhydroceles/spermatoceles larger than 175 ml, 58% and 34% were cured after thefirst treatment in the 4 and 2 ml groups, respectively (p � 0.012), with nodifferences in complications between the groups.Conclusions: Polidocanol sclerotherapy was effective for the treatment of hydro-cele or spermatocele in our patients, with 94% satisfactory results after 1 to 4treatments. A dose of 4 ml was superior to 2 ml, particularly for largerhydroceles/spermatoceles.

Submitted for publication January 24, 2011.Study received local ethics committee ap-

proval.Nothing to disclose.* Correspondence: Department of Urology,

University Hospital, SE-58185 Linköping, Sweden(telephone: �46-13222000; FAX: �46-13224574;e-mail: Staffan.Jahnson@lio.se).

Editor’s Note: This article is the

third of 5 published in this issue

for which category 1 CME credits

can be earned. Instructions for

obtaining credits are given with

the questions on pages 1562 and

1563.

Key Words: polidocanol, sclerotherapy, testicular hydrocele, spermatocele

RADICAL surgery has been the standardtreatment for hydrocele and spermato-cele, but in recent decades sclerother-apy has been increasingly used andadvocated as a minimally invasive pro-cedure.1,2 Many different sclerosingagents have been used, most often phe-nol, sodium tetradecyl sulfate, polido-canol or tetracycline.1–11 Sigurdsson etal compared the cited studies and foundthat a wide range of doses of a broad

array of sclerosing agents had been

0022-5347/11/1864-1319/0THE JOURNAL OF UROLOGY®

© 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RES

used, with results varying consider-ably.11 Tetracycline or polidocanol re-sulted in primary cure rates of 45% to85%, whereas the corresponding fig-ures for sodium tetradecyl sulfate, phe-nol and other sclerosants were in therange of 36% to 52%. Complications oftreatment included pain, hematomaand epididymitis, but the implicationsof these problems for the patients werenot always clearly stated. In 1 of the

investigations polidocanol was found to

Vol. 186, 1319-1323, October 2011Printed in U.S.A.

EARCH, INC. DOI:10.1016/j.juro.2011.06.005www.jurology.com 1319

POLIDOCANOL SCLEROTHERAPY FOR HYDROCELE/SPERMATOCELE1320

be the optimal sclerosing agent, offering the combina-tion of treatment efficiency and a low complicationrate.2

Thus, it seems that sclerotherapy is the treat-ment of choice for hydroceles and spermatoceles,and polidocanol appears to be one of the most effi-cient sclerosing agents. However, the optimal dose ofpolidocanol is not known and, therefore, we con-ducted a double-blind randomized study to comparethe effects of 2 and 4 ml polidocanol (30 mg/ml) forsclerotherapy.

MATERIALS AND METHODS

The study was conducted in Sweden from 1993 to 2005.Participation was offered to all patients presenting withhydrocele or spermatocele at the Department of Urology ofUniversity Hospital in Örebro (1993 to 1999), and later toall patients at the Departments of Urology at UniversityHospital in Linköping (1999 to 2005) and SahlgrenskaUniversity Hospital in Göteborg (2003 to 2005). The ex-clusion criteria consisted of previous surgery or sclerother-apy for hydrocele or spermatocele, previous hernia sur-gery, ongoing clinical epididymitis, age younger than 40years or desire to have children. Only a small proportion ofthe patients refused to participate and the study wasapproved by the local ethics committee.

The study protocol included a power calculation assum-ing that increasing the volume of polidocanol would resultin an increase in primary cure from 46% in the low volumegroup to 66% in the high volume group. This would re-quire 200 patients (100 in each treatment arm) given apower of 0.8. The length of the study period reflected theeffort to randomize a sufficient number of patients. Nointerim analyses were planned or performed.

Treatment ProcedureUnder aseptic conditions the scrotum was illuminated tolocate an avascular area corresponding to the fluid collec-tion, which was usually found in the cranial and ventralpart of scrotum. According to the decision of the treatingurologist, the skin was or was not anesthetized using 5 to10 ml lidocaine (Xylocaine® 10 mg/ml). A 17 gauge intra-venous cannula was introduced into the swelling and thefluid was completely evacuated. An assisting nurse ad-ministered 2 or 4 ml polidocanol (Aethoxysklerol® 30 mg/ml), according to the results of randomization from closedenvelopes. The amount of polidocanol given was not shownto the urologist or the patient. After injection, the cannulawas withdrawn and the scrotal content was palpated todistribute the polidocanol over the entire wall of the hy-drocele or spermatocele. Palpation was also performed todetect testicular lesions or nodes in the epididymis with orwithout tenderness.

In most patients the evacuated fluid was examined bymicroscopy for spermatozoids. A hydrocele had yellowishspermatozoid-free fluid that surrounded the testis,whereas a spermatocele had opalescent spermatozoid con-taining fluid located cranial to the testis. In 32 cases (14%)the fluid was not examined under a microscope, and clas-

sification as spermatocele or hydrocele was done solely by

considering the fluid with regard to macroscopic charac-teristics and location in relation to the testis and epidid-ymis. In a few cases a multilocular spermatocele wasfound and handled using the same cannula for simultane-ous puncture of all celes. Polidocanol was injected into themain compartment.

FollowupPatients were scheduled for a followup visit 3 to 4 monthsafter initial polidocanol and the treatment was repeated ifthere was a recurrence of fluid at that time. All patientswere recommended to repeat treatment until there was noresidual fluid but some refused because they were satis-fied when only a small amount of fluid remained. Treat-ment results were considered satisfactory in patients whowere cured or had only a small amount of residual fluid. Adecision to proceed to further sclerotherapy or surgerywas made after discussion between the patient and thetreating urologist.

To register complications and side effects the patientswere asked to complete a self-administered questionnairethat reported problems such as pain and scrotal edema,and to return it at the followup visit. Furthermore, pa-tients were told to contact the department if they experi-enced any symptom that did not respond to self-medica-tion, especially fever, pain or discomfort. In most patientssuch symptoms involved a swollen epididymis with littleor no particular tenderness, although in the rare casesthat entailed more pain, the condition was considered tobe an epididymitis, and was treated accordingly with an-tibiotics and nonsteroidal anti-inflammatory drugs.

DefinitionsA spermatocele was defined as having opalescent fluidthat contained spermatozoids and was located cranial tothe testis. A hydrocele contained spermatozoid-free yel-lowish fluid that surrounded the testis. Cure was definedas generally no fluid present, but occasionally a smallamount was observed (ie less than 10 ml and less than10% of initial fluid). A small amount of residual fluid wasdefined as less than 40 ml and less than 10% of the initialamount. An unsatisfactory outcome indicated that pa-tients underwent surgery, left with more than a smallamount of fluid or were lost to followup. Epididymitis wasdefined as a swollen epididymis found at a scheduledfollowup visit or at an emergency visit due to acute prob-lems and, thus, it may or may not be accompanied by painand/or fever. Most of the observed cases of epididymitiswere of low or moderate intensity. Low intensity wasdefined as pain or discomfort without the need for anymedication. Moderate intensity was defined as more painor discomfort requiring self-medication and/or nonurgentcontact for visit and medication. High intensity was de-fined as pain or other symptoms leading to emergencycontact for evaluation and treatment.

RESULTS

A total of 232 patients were randomized to the studybut 8 had less than 40 ml fluid at puncture and,therefore, were excluded from analysis according to

the treatment protocol. The remaining 224 patients

POLIDOCANOL SCLEROTHERAPY FOR HYDROCELE/SPERMATOCELE 1321

had hydroceles (67%) or spermatoceles (33%) as pre-viously defined. Cure after the first treatment wasobserved in 120 (54%) of the patients and 210 (94%)had satisfactory results after all treatments. Treat-ment failure was often due to patients refusing fur-ther treatment or choosing some other form of treat-ment (ie surgery). Complications consisting of pain,discomfort and a swollen scrotum/epididymis oc-curred in 55 patients, and 49 (89%) complicationswere essentially of low or moderate intensity. Epi-didymitis was treated for 3 weeks with antibioticsand nonsteroidal anti-inflammatory drugs, whichgenerally led to resolution of pain within 1 or 2 daysand normalization of the swollen epididymis within1 to 3 months, although a small nontender noduleremained in the epididymis in a few cases.

Characteristics of the patients and hydroceles/spermatoceles in relation to treatment groups aresummarized in table 1. Cure after the first treat-

Table 1. Patient characteristics and results of sclerotherapy

2 Ml 4 Ml p Value

No. pts 113 111Median pt age (range) 65 (41–95) 62 (42–88) Not significantMedian ml vol emptied

(range)180 (40–900) 175 (40–550) Not significant

Median mos from onset(range)

24 (1–240) 24 (1–240) Not significant

No. missing (%) 9 (8) 8 (7)No. swelling type (%):

Hydrocele 76 (68) 74 (66) Not significantSpermatocele 37 (32) 37 (34)

No. swelling side (%):Rt 64 (57) 59 (53) Not significantLt 49 (43) 52 (47)

No. complication type (%):None 92 (81) 77 (69) 0.04Discomfort/pain 19 (17) 14 (13)Hematoma 0 2 (2)Epididymitis 2 (2) 18 (16)

No. complication intensity(%):

No complication 92 (81) 77 (69) 0.04Low 12 (11) 8 (7)Moderate 9 (8) 20 (18)High 0 6 (5)

No. cure after 1 treatment(%):

Yes 53 (47) 67 (59) 0.04No 60 (53) 44 (41)

No. No. treatments (%):1 58 (51) 68 (62) Not significant2 40 (35) 35 (31)3 or More 15 (14) 8 (7)

No. results of all treatments(%):

Cure 100 (88) 100 (90) Not significantSmall residual fluid 7 (6) 3 (3)Surgery 4 (4) 3 (3)Lost to followup/large

fluid3 (2) 5 (5)

ment was more common in the 4 ml than in the 2 ml

polidocanol group (chi square 4.4, p � 0.04), andcomplications occurred in more patients in the 4 mlgroup (chi square 4.1, p � 0.04). Complications wereof low intensity and did not require any medicationin 20 (36%) of the patients, and they were of moder-ate intensity in 29 (53%), who had more pain ordiscomfort that was managed with self-medicationand/or nonurgent contact for visit and medication.All patients with high intensity complications neces-sitating urgent medication or hospitalization hadreceived sclerotherapy with 4 ml polidocanol. Ofthose patients 1 had an emergency operation for aswollen and painful scrotum, and was found to haveepididymitis.

Recurrence of fluid was seen at first followup visitwithin 3 to 4 months or was not seen at all. Sclero-therapy was repeated once in 35% and 31% of thepatients in the 2 ml and the 4 ml group, and 3 ormore treatments were necessary in 14% and in 7%,respectively. In general the rates of satisfactory re-sults after all treatments did not differ substantiallybetween the groups (table 1).

However, in patients with larger collections (morethan 175 ml fluid), the results varied more exten-sively between the 2 treatment groups. Cure afterthe first treatment was more common in the 4 mlgroup (58%) than in the 2 ml group (37%, chi square6.3, p � 0.01). No significant difference between thegroups was found with regard to the rate of compli-cations after the first polidocanol treatment (chisquare 3.1, p � 0.08) or concerning satisfactory re-sults after all treatments (data not shown).

Logistic regression analysis showed that cure af-ter the first treatment was more common in patientswith a time from onset of 24 months or less vs thosewith a longer time from onset, as well as in the 4 mlcompared to the 2 ml group. No difference in pri-mary cure was observed with respect to age, type ofswelling, side of swelling or amount of fluid in theswelling (table 2). Another logistic regression anal-ysis showed that complications were not associatedwith age, type of swelling, side of swelling, time fromonset or volume of fluid. There were more complica-tions in the 4 ml than in the 2 ml polidocanol group,but this difference was not statistically significanton multivariate analysis.

DISCUSSION

This prospective randomized study was conductedover a long period to enroll the required number ofpatients. Nevertheless, the hypothesis of the studywas rejected as the difference in primary cure ratesbetween the 2 treatment groups was less than 20%.Given the actual observed cure rates the study wasobviously underpowered but the hypothesis might

have been accepted with a higher number of pa-

POLIDOCANOL SCLEROTHERAPY FOR HYDROCELE/SPERMATOCELE1322

tients randomized or inclusion of only swellings con-taining more than 175 ml fluid.

However, the results of the present study indicatethat sclerotherapy using polidocanol (30 mg/ml) wasmore efficient when 4 ml was injected than when 2ml was administered, and this effect was particu-larly prominent in cases involving larger celes con-taining more than 175 ml fluid. One to 4 treatmentsled to satisfactory results in more than 90% of thepatients in both groups, which suggests that bothdoses of polidocanol are excellent choices for sclero-therapy of hydrocele or spermatocele. These resultsagree well with previous studies using other scleros-ing agents, which indicates that polidocanol is one ofthe most effective drugs for sclerotherapy.2–8

Similarly the rate and the intensity of complica-tions of polidocanol were low in our study comparedto results reported for other sclerosing agents,2–8

which favors the use of polidocanol. In our series36% of the complications were of low intensity andrequired no medication. Only occasional medicationwas needed in 29 patients (53%) whose complica-tions were of moderate intensity. Furthermore, thecases involving high intensity complications were

Table 2. Multivariate logistic regression analyses of variablesof importance after the first polidocanol sclerotherapy

Recurrence OR (95% CI) Complications OR (95% CI)

Age:65 or Younger 1.00 1.00Older than 65 0.74 (0.42–1.29) 0.65 (0.34–1.23)

Mos from onset:24 or Less 1.00 1.00Greater than 24 1.91 (1.06–3.47)* 0.80 (0.40–1.57)Not known 1.55 (0.60–4.83) 0.16 (0.02–1.29)

Side:Lt 1.00 1.00Rt 1.00 (0.55–1.81) 1.10 (0.55–2.18)

Type of swelling:Spermatocele 1.00 1.00Hydrocele 1.53 (0.88–2.68) 1.10 (0.58–2.09)

Ml fluid vol:175 or Less 1.00 1.00Greater than 175 1.66 (0.94–2.92) 0.69 (0.31–1.13)

Ml polidocanol:2 1.00 1.004 0.56 (0.32–0.97)* 1.87 (0.99–3.53)

Recurrence or complications after the first treatment were thedependent variables.* Statistically significant difference.

resolved after 2 to 3 weeks of medical treatment.

REFERENCES

The rate of complications in the present series washigher than that reported by Sigurdsson et al11 butlower than rates reported by Lund and Bartolin9

and Gasser et al,10 which indicates that the occur-rence of complications varies even when the samesclerosing agent is used. This variation raises thequestion of how complications were recorded inthe mentioned investigations and what criteria wereused to define an event as a complication of sclero-therapy. In the present study we used a self-adminis-tered questionnaire about complications, and our pa-tients were encouraged to contact the department foremergency evaluation by the treating urologist if theyexperienced problems. Apparently this was not theprocedure in most of the other investigations.2–11

According to Braslis and Moss,12 and Stattin etal,13 once a hydrocele/spermatocele is cured, there islittle risk of recurrence over time. This finding is inagreement with our observation that none of thepatients with a cured cele returned for further ther-apy due to recurrence on the treated side during the12-year study period or the 2-year followup of thelast randomized patient.

Daehlin et al compared the use of polidocanol andtetracycline as sclerosing agents, and found that 1treatment led to cure in 53% of the patients whoreceived polidocanol and 85% of those given tetracy-cline.14 However, there were more complications inthe latter group. The authors recommended multi-ple injections of polidocanol as the treatment ofchoice. Other researchers compared open surgeryand sclerotherapy using phenol in a retrospectiveseries15 and antazoline, or sodium tetradecyl sul-fate, in small randomized series.16,17 In those stud-ies sclerotherapy resulted in cure rates comparableto those achieved with surgery, but it was associatedwith lower morbidity and fewer complications. No-tably the cost of sclerotherapy has also been re-ported as approximately 10% of the cost of surgeryin cases involving hydrocele or spermatocele.15,18

In conclusion, our findings suggest that sclerother-apy using polidocanol or other efficient sclerosingagents should be considered for scheduled treatmentof hydrocele or spermatocele on 1 to 4 occasions be-cause that approach can give a cure rate equivalent tothat offered by surgical treatment. Indeed, it seemsthat such scheduled sclerotherapy can be just as effi-cacious as surgery, but it is associated with lower

morbidity and lower costs.

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