JOURNAL OF ENDOUROLOGY
Volume 20, Number 1, January 2006
© Mary Ann Liebert, Inc.
Medical Expulsive Treatment of Distal-Ureteral Stones Using
Tamsulosin: A Single-Center Experience
MARCO DE SIO, M.D., Ph.D., RICCARDO AUTORINO, M.D., FEBU, GIUSEPPE DI LORENZO, M.D.,
ROCCO DAMIANO, M.D., DARIO GIORDANO, M.D., LUCA COSENTINO, M.D., UMBERTO PANE, M.D.,
FERDINANDO DI GIACOMO, M.D., SALVATORE MORDENTE, M.D., and MASSIMO D’ARMIENTO, M.D.
Purpose: To evaluate the efficacy of the addition of tamsulosin to our standard expulsive pharmacologic ther-
apy for the treatment of distal-ureteral stones.
Patients and Methods: A series of 96 patients referred to our department for the management of sympto-
matic distal-ureteral calculi were randomly divided into group 1 (N ? 46) who received diclofenac (100
mg/daily) plus aescin (80 mg/daily) and group 2 (N ? 50) who received the same therapy plus tamsulosin (0.4
mg/daily) for a maximum of 2 weeks. There were no differences between the groups with respect to age, sex,
or stone size. The primary endpoint was the expulsion rate. Expulsion time, need for analgesics, need for hos-
pitalization, and drug side effects were the secondary endpoints.
Results: The expulsion rate was significantly higher in group 2 (90%) than in group 1 (58.7%; P ? 0.01),
and group 2 achieved stone passage in a shorter time (mean 4.4 v 7.5 days, respectively; P ? 0.005). Lower
analgesic use was found in group 2 (P ? 0.003), as well as significantly fewer hospitalizations for recurrent
colic (P ? 0.01). Both groups experienced few side effects associated with expulsive therapy.
Conclusions: A conservative approach should be considered as an option in the management of uncompli-
cated distal-ureteral stones. Even if the best pharmacologic expulsive regimen remains to be established, the
use of the selective ?-blocker tamsulosin is recommended in this setting.
ated in the management of patients with lower urinary-tract
symptoms (LUTS) caused by different urologic conditions.1
Urinary stones still represent an important topic in everyday
urologic practice, as it has been reported that as many as 15%
of the population in Western countries suffers from this dis-
ease.2Renal colic is one of the most painful conditions that may
occur and is often caused by ureteral stones, most of them be-
ing located in the distal part of the ureter.3
Minimally invasive therapies, such as SWL and uretero-
scopy, allow distal ureterolithiasis to resolve in almost all cases.
On the other hand, the role of medical expulsive therapy in the
management of this condition is still unclear. Moreover, the
most effective pharmacologic regimen for encouraging stone
HE SELECTIVE ?1A/?1D-ADRENOCEPTOR ANTAGO-
NIST tamsulosin has proved be effective and well toler-
expulsion has not been yet determined despite the recognized
Several factors are associated with calculi retention includ-
ing ureteral-muscle spasm, submucosal edema, pain, and in-
fection. It seems logical that conservative therapy should ad-
dress these factors. Some groups have implemented an
observational approach based only on the control of pain, while
others treat the stone retention pharmacologically in order to
facilitate stone expulsion.5–7
?1-Receptors are the most abundant adrenergic receptors in
ureteral smooth-muscle cells. The blockade of ?-adrenergic re-
ceptors by a specific antagonist inhibits basal tone, peristaltic
activity, and ureteral contractions.8,9
?1-Adrenergic receptors have been divided in four groups,
with a1D being found mostly on the lower intramural portion of
the ureter where it passes through the detrusor muscle.10Based
on this findings, different groups have tried the selective
Department of Urology, Second University, Naples, Italy.
?1A/?1D-adrenoceptors antagonist tamsulosin in the treatment
of distal-ureteral calculi and obtained encouraging results.11–13
We evaluated the addition of tamsulosin to our standard med-
ical expulsive therapy for this pathological condition.
PATIENTS AND METHODS
A series of 96 patients referred to our department for the
management of symptomatic 10-mm or smaller stones in the
distal segment of the ureter (juxtavesical tract and ureterovesi-
cal junction) were prospectively included. The exclusion crite-
ria were urinary-tract infection, severe hydronephrosis, dia-
betes, ulcer disease, hypotension or hypertension treated with
a-blockers or calcium antagonists, pregnancy, multiple stones,
history of spontaneous stone expulsion, or ureteral stricture. All
stones were diagnosed with unenhanced CT scans. The patients
were randomly divided into two groups. Group 1 (N ? 46) re-
ceived diclofenac (100 mg/daily) plus aescin, an anti-edema ex-
tract of the horse chestnut tree (80 mg/daily), and group 2 (N ?
50) received the same therapy plus tamsulosin (0.4 mg/daily)
for a maximum of 2 weeks. There were no differences between
the groups with respect to age, sex distribution, or stone size
(Table 1). All patients were instructed to drink 2 L of water
daily. All received 20 mg omeprazole daily for the treatment
period and 250 mg of levofloxacin daily for the first week. The
treatment was fully explained to the patients, and all provided
valid informed consent.
The follow-up continued until the stone was passed or in-
tervention occurred (SWL or ureteroscopy). The criteria for
treatment discontinuation as well as the need for hospitaliza-
tion and/or endoscopic treatments were uncontrollable pain,
fever, or severe hydronephrosis and failure of stone expulsion
after 2 weeks.
The expulsion rate was the primary endpoint of the study.
Expulsion time, need for analgesics, need for hospitalization,
and drug side effects were the secondary endpoints. Treatment
was assigned on a randomized basis according to a 1:1 ratio.
Randomization was performed using a stratified permuted al-
gorithm. All randomly assigned patients were included in the
efficacy and safety analysis. As it could represent a source of
bias, only two investigators, both of whom were blinded to the
initial randomization and treatment, decided on the need for
hospitalization or intervention.
The Student t-test was used to compare the means of nor-
mally distributed variables in the two treatment groups. Other-
wise, the Mann-Whitney U test was used. Nominal parameters
were analyzed using Fisher’s exact test. SPSS software was
used to perform the statistical analysis.
The stone expulsion rate was 58.7% (27 of 46 patients) in
group 1 and 90% (45 of 50) in group 2 with a mean expulsion
time of 7.5 ? 1.8 and 4.4 ? 2.1 days, respectively (Fig. 1).
Group 2 showed a statistically advantage in terms of both ex-
pulsion rate (P ? 0.01) and expulsion time (P ? 0.005).
No significant difference in mean stone size was found in
either group between patients who were and those who where
not stone free (5.7 ? 1.2 and 6 ? 1.4 mm, respectively; P ?
0.05). Similarly, no difference was observed in the distribution
of expulsion by sex (P ? 0.05).
Group 2 required significantly less analgesic than group 1
(10% v 37%; P ? 0.003) (Table 2). Similarly, hospitalization
for recurrent colic was required in 27.5% of the patients in group
1 (11 of 46) and, among them, 6 patients needed an endoscopic
maneuver to put in a stent because of uncontrollable pain. In
group 2, only 5 patients were hospitalized (10%; P ? 0.01), and
none of them required ureteral stenting during the observation
period (Table 2).
Minor side effects associated with expulsive therapy were
experienced by a few patients in both group 1 and 2 (4.3% and
6%, respectively; P ? 0.05). None of them resulted in treat-
ment discontinuation. In group 1, there were three case of
malaise and one case of diarrhea. In group 2, there were two
patients with transient hypotension and one with asthenia and
dizziness. No stomach ache was recorded (Table 2). Patients
(19 in group 1 and 5 in group 2) who were not stone free after
the 2 weeks of follow-up were treated successfully with
ureteroscopy or SWL.
Minimally invasive therapies such as SWL and ureteroscopy
have been widely adopted during recent years for the treatment of
ureteral stones. Their efficacy has been demonstrated by several
studies, even if these procedures are not free of risk and inconve-
niences.14Moreover, even a simple watchful waiting approach can
result in complications affecting renal function. According to lit-
erature data, the expulsion rate of distal-ureteral stones produced
by a watchful waiting approach is 25% to 54% with a mean ex-
pulsion time of ?10 days and considerable analgesic use.2–4
TAMSULOSIN FOR URETERAL STONES
TABLE 1.DEMOGRAPHIC DATA OF TWO GROUPSa
Group 1 (N ? 46)Group 2 (N ? 50)
Mean age ? SD
size ? SD (mm)
44.5 ? 11.346.3 ? 10.9
6.4 ? 1.3
6.9 ? 1.0
aNone of the differences is statistically significant.
Expulsion rate (%)*
Group 1 Group 2
Mean expulsion time (days)**
0.01; **P ? 0.005.
Expulsion rate and time according to treatment. *P ?
The inability to control pain is usually the indication for ac-
tive treatment of ureteral stones. The causes of colicky pain are
the strain on muscular nerve endings and mucosa, which is
caused by the increase in intraluminal pressure secondary to the
inability of ureteral peristalsis to move the urine distal to the
The main factors associated with obstruction by stones are
ureteral-muscle spasm, submucosal edema, pain, and infection
within the ureter. It seems logical that medical therapy address
these factors. Various drug combinations have been described
to assist the passage of ureteral stones, as several drugs can in-
fluence the contractile activity of the ureter. Calcium-channel
blocking agents and steroids have commonly been used to re-
duce muscular tone and decrease inflammation. Borghi and col-
leagues5used an expulsive therapy consisting of methylpred-
nisone and nifedipine in a randomized double-blind study,
treating patients with ureteral stones as large as 1.5 cm. They
demonstrated a beneficial effect in reducing the time to stone
passage and improving the expulsion rate. Their results were
confirmed by Porpiglia et al,7who used nifedipine plus another
corticosteroid agent, deflazacort. Cooper and associates6treated
70 patients having ureteral calculi and found that the addition
of nifedipine, prednisone, acetaminophen, and antibiotics to
their standard medical therapy resulted in much higher stone-
passage rate and fewer work days lost, emergency room visits,
and surgical interventions. However, those investigators un-
derlined how difficult it was to quantify the contribution of each
drug to the outcome of treatment. Moreover, although having
some effect on pain and stone movement, these drugs also have
severe side effects. Headache and asthenia may be mild, but
hypotension and palpitations can result in treatment discontin-
Because ?1receptors are predominant in the ureteral smooth
muscle,8it has been suggested that the blockade of such re-
ceptors by a specific antagonist will decrease ureteral peristaltic
activity with a consequent loss of intraureteral pressure and an
increase in fluid transport ability.9Therefore, the use of a-block-
ers with the aim of facilitating lower-ureteral stone expulsion
has been advocated in this setting. Ukhal and coworkers15were
the first to report positive results in accelerating lower-ureteral
stone passage using an ?-blocker agent. They found that the
rate of spontaneous passage of distal-ureteral stones during
treatment with doxazosin was 71.1%, and they emphasized that
the treatment decreased the frequency of renal colic.
More recently, it has been demonstrated10that specific
adrenoceptor subtypes (?1A/?1D) are prevalent in the distal part
of the ureter, and this finding supported the interesting results
obtained by different groups with the use of tamsulosin in the
treatment of selected distal-ureteral calculi. Cervenakov and
colleagues11performed a randomized study and registered a sig-
nificant advantage in stone-expulsion rates when adding tam-
sulosin to their standard therapy, which was actually complex,
DE SIO ET AL.
TABLE 2.RESULTS ACCORDING TO DRUG REGIMEN
No. of pts. (%) Group 1 (N ? 46)Group 2 (N ? 50)
TABLE 3.TAMSULOSIN ARMS IN RANDOMIZED STUDIES ON TREATMENT OF URETERAL STONES
0.4 mg plus . . .
(No. of pts.)
rate (%) Series
51 5.8Tramadol (50 mg),
diazepam (5 mg),
veral (150 mg),
yellow (120 mg)
Deflazacort (30 mg),
(640 mg), diclofenac
(75 mg on demand)
Deflazacort (30 mg),
diclofenac (75 mg
Diclofenac (100 mg)
28 5.44 85 7.72
15 4.72 53—1
29 6.0Diclofenac (75 mg
Diclofenac (100 mg),
aescin (80 mg),
consisting of tramadol, diazepam, veram (nonsteroidal anti-in-
flammatory) and yellon (anti-exudative). In their first report on
this topic, Dellabella et al12found greater efficacy with tamsu-
losin, which was compared with phloroglucinol, a spasmolytic
drug very popular in Italy. Interestingly, these authors explained
the positive effect of tamsulosin: it should induce an increase
in the intraureteral pressure gradient around the stone as well
as a decrease of the frequency of peristaltic contractions in the
obstructed ureter and therefore a reduction of the algogenic
stimulus. More recently, the same group published their up-
dated data on 210 patients in order to compare the efficacy of
three drugs (nifedipine, tamsulosin, and phloroglucinol) for the
spontaneous expulsion of distal-ureteral stones. They found the
highest expulsion rate in the tamsulosin group (97.1% v 64.3%
in the phloroglucinol group and 77.1% in the nifedipine group).
Moreover, the tamsulosin group achieved stone passage in a
significantly shorter time and with fewer hospitalizations, as
well as a decrease in the need for endoscopic procedures. There-
fore, those investigators advocated the use of tamsulosin as a
first-line approach for the in-home management of patients with
distal-ureteral stones.16A very interesting new issue in this pa-
per from Dellabella et al is the way they try to explain why pa-
tients treated with tamsulosin experienced significantly less
pain than those treated with nifedipine. In fact, they suppose a
double action of tamsulosin on the control of pain associated
with ureteral colic, one on the smooth muscle, preventing
spasm, and a second on C-fibers or sympathetic postganglionic
neurons, which also blocks pain conduction to the central ner-
Porpiglia and associates13compared the safety and effec-
tiveness of nifedipine and deflazacort with those of tamsulosin
and deflazacort for the treatment of distal-ureteral stones. They
concluded that medical therapy, particularly with tamsulosin,
could reduce expulsion times. Kupeli and coworkers17reported
their experience with the addition of tamsulosin to medical ther-
apy or to SWL for lower-ureteral stones. They randomized 78
patients into four groups, all being reevaluated after 2 weeks.
The difference in the stone-free rates of the tamsulosin and con-
trol groups was statistically significant. The positive effect of
the ?-blocker was more evident for larger stones..
Finally, Yilmaz et al18were the first to perform a random-
ized comparison of three a1-blockers in the treatment of distal-
ureteral stones. They enrolled 114 patients, who received noth-
ing, tamsulosin, terazosin, or doxazosin for as long as 1 month.
All three agents were equally efficacious. Moreover, those au-
thors underlined the fact that no steroids were used, an impor-
tant feature of their study.
In the present study, patients were randomized to receive our
standard therapy (diclofenac sodium plus aescin plus antibiot-
ics) or standard therapy plus a selective ?1A/?1D-adrenoceptor
antagonist (tamsulosin). Our specific aim was to evaluate the
potential role of tamsulosin in our standard medical approach
for the conservative treatment of distal-ureteral stones.
It is our belief that a conservative approach to ureteral
stones up to 10 mm should not be proposed for longer than
2 weeks in order to avoid renal function impairment, urosep-
sis, and intractable pain. This period is shorter than the 4
weeks proposed by Hubner et al19and adopted by most other
investigators. A placebo was not used in the control group
because our main goal was to compare tamsulosin with our
standard therapy. Moreover, it would have been difficult to
offer a placebo when the passage of the stone is invariably
associated with colicky pain that represents a major problem
for the patient.
Because it is widely recognized that infection within the
ureter is a possible cause of calculus retention, it seemed ad-
visable to include an antibiotic in the standard approach to the
patient with a symptomatic ureteral stone. We thought that 1
week of levofloxacin 250 mg could be an appropriate and rea-
sonable measure in this setting. Similarly, in the study by Della-
bella et al,12patients received cotrimoxazol only for 8 days,
whereas in the one by Cooper and associates,6they received
trimethoprim–sulfa for 7 days.
Diclofenac sodium is a nonsteroidal anti-inflammatory drug
(NSAID) advocated for use in painful conditions. It possesses
potent analgesic properties with a fast onset and long duration.
It has already been proposed that pain relief, together with spas-
molysis of the ureter supporting stone passage, can be achieved
by application of an NSAID such as diclofenac.20
Aescin, the major active principle from the horse chestnut
tree, has shown satisfactory evidence of a clinically significant
activity in postoperative edema. Its therapeutic benefit is well
supported by a number of investigations indicative of clear-cut
anti-edematous, anti-inflammatory properties and excellent tol-
The patients in the tamsulosin group demonstrated a higher
incidence of stone passage (90% v 58.7%) and more rapid stone
passage (4.4 v 7.5 days). We observed only 3 cases of minor
side effects in the tamsulosin group, which confirms the safety
and tolerability of the drug. Although our side-effect profile for
tamsulosin seems low compared with published data, you have
to consider that our results are after only 2 weeks of treatment.
Regarding retrograde ejaculation, none of the male patients re-
ported any abnormality, probably, again, because of the short
observation time and the decrease in coitus frequency owing to
colicky pain. Our results are comparable to those of other
groups (Table 3).
Tamsulosin showed efficacy comparable to that of ureteros-
copy for removing the stone, thus offering excellent pain relief,
as shown by significantly lower use of analgesics (10% v 37%).
In addition, tamsulosin drastically decreased the need for hos-
pitalization (10% v 27.5%) as well as the need for endoscopic
procedures (0 v 13%). Thus, these results determined the pos-
sibility of home management and allowed the patient to per-
form everyday activities almost regularly, which means an
advantage in terms of cost. In this respect, it has been demon-
strated that a conservative approach is associated with reduced
expenses only if successful.14
A conservative approach should be considered as an option
in the management of uncomplicated distal-ureteral stones.
Even if the best pharmacologic expulsive regimen remains to
be established, the use of the selective alpha-blocker tamsulosin
is recommended because of its high efficacy, minimum side ef-
fects, and excellent patient satisfaction. Further clinical research
in this field is warranted, and larger multicenter trials are
TAMSULOSIN FOR URETERAL STONES
CONTRIBUTIONS TO THE STUDY
M. Sio contributed to the study design and was responsible
for the randomization; M. D’Armiento coordinated the study
and critically reviewed the manuscript; G. Di Lorenzo per-
formed statistical analysis; S. Mordente and R. Damiano had a
major role in data analysis; L. Cosentino, U. Pane, and F. Di
Giacomo selected the patients and were responsible for the fol-
low-up; R. Autorino contributed to the study design and wrote
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Address reprint requests to:
Riccardo Autorino, M.D., FEBU
Vico Santo Spirito 54
80132 Naples, Italy
DE SIO ET AL.