A total of 246 patients were assessed for eligibility of which 135 patients were selected as study population. Among them 7 patients were withdrawn before randomization due to non-cooperation. The remaining 128 patients were randomly allocated into Group A consisted of 64 patient and Group B of 64 patients. During the study period 4 patients from Group-A and 4 patients from Group-B discontinued the intervention. Hence, they were dropped out and finally results of 60 cases from each group were compared. The mean age (±SD) for group A was 38.5 (SD±10.05) years (age range 18-60 years) and for Group B was 37.7 (SD±9.33) years (age range 18-59 years). Age of the patients of each group were compared and found no significant difference (table I).
In Group-A, 19 (31.7%) patients were in stone size between 3 to 5 mm and 41(68.3%) patients were in stone size between 6 to 8mm. In Group-B, 18 (30%) patients were in stone size between 3 to 5 mm and 42 (70%) patients were in stone size between 6 to 8 mm. In both groups, the distribution of stone size showed no statistical significance (table II).
In group A and B rate of stone expulsion from the ureter were 53.3% cases and 85.0% cases respectively. There was significant difference in clearance of stone between the groups (table III), but the rate of expulsion varies according to size shown in Figure 1 and Figure 2.
The mean episodes of pain in patients of Group A and Group B were respectively 4.13±1.704 and 2.58±1.519, shown in table IV;
±0.05). In group A and B urinary tract infection was detected in 20% and 3.33% patients respectively and the difference was statistically significant (
Discussion
Though there is no exact data about the prevalence of ureterolithiasis in Bangladesh but the problem is quite common. Multimodalities of treatment are available to the urologists. Minimal invasive therapies such as extracorporeal shockwave lithotripsy and ureteroscopy have been widely introduced for treatment of ureteric stones during last two decades.
12 The efficacy of these treatments has been proved by several studies.
13 However, although such procedures are rather effective, they are not free of risk or inconveniences and are quite expensive.
5On the other hand, conventional treatment like simple watchful waiting approach with two litres of daily water intake can result in complications such as urinary tract infection, repeated colicky pain or hydronephrosis and can affect renal function.
12
However, this treatment may not always be sufficient, especially for stones located at the intramural ureter, where smooth muscle tonus is more evident.
13 Studies have revealed that alpha
1-adrenergic receptors are the most abundant receptors in ureteral smooth muscle cells and alpha
1-adrenergic antagonists inhibit basal tone, peristaltic activity and ureteral contractions.
8 Generally, the main obstacle to the transport of lower ureteral stones is the intramural detrusor tunnel;
7 thus, blocking these receptors could affect stone passage. Tamsulosin is a competitivealpha
1-adrenergic antagonist having higher affinity for alpha
1A and alpha
1D adrenoceptors.These receptors are located in smooth muscle of prostate, bladder neck, detrusor, vesicoureteric junction and ureter specially lower part.
12 The blockade of alpha adrenergic receptor by a specific antagonist like Tamsulosin results in decreased ureteralperistaltic amplitude and frequency with a consequent loss of intraureteral pressure and thereby an increase in fluid transport ability. Thus the effect of Tamsulosin on the obstructed ureter is to induce an increase in the intramural perssure gradient around the stone as well as decreased peristalsis below the ureter and consequently a dcrease in intramural pressure below the stone in association with the decrease in basal and micturition pressure even at the bladder neck. All these mechanisms bolster the urge to expel the stone.
11,16
The present study was designed to prove the efficacy of Tamsulosinin addition to conventional treatment for the management of juxtavesical ureteric stone having size up to 8 mm. A total of 120 patients were grouped into two on alternate basis, 60 patients in group A treated with conventional therapy consists of hydration, physical exertion and analgesics.
60 patients of group B were given Tamsulosin 0.4mg daily along with the conventional treatment. Therapies in both groups continued for 4 weeks or until stone expulsion within 4 weeks. In complete obstruction, the signs of renal injury appear in three to four weeks. For this reason, the spontaneous passage of stones can be waited on for 4 weeks.
3 The mean age with SD in Group-A and Group-B were 38.55±10.05 and 37.7±9.33 years. No significant difference was observed among the two groups in relation to age and sex. This creates an equal group, so that these didn't cause any effect to the outcomes.
In this study, mean stone size was 5.88±1.23 mm (range 3-8) for Group-A and 5.94±0.92 mm (range 3.5-8) for Group-B. There was no significant difference between two groups with respect to stone size. The above distribution correlates with the study done by Cervenakov et al
14 having stone size between 3-10 mm in each group but does not correlate with the study conducted by Dellabella et al
11 having stone size 4-11mm and 3.8-13 mm in conventional and Tamsulosin group respectively.
Episodes of pain in this study was statistically significantly lower in Group-B patients compared to Group-A (
p <0.05). Mean episodes of pain in patients of Group-A was 4.13± 1.704 and that in Group-B was 2.58± 1.519.Patients in the study by Yilmaz E et al12 suffered from pain episodes of 2.42±1.39 and 1.72±0.88 without and with Tamsulosin respectively.
In the current study, stone expulsion occurred in 83(69.2%) of 120 subjects enrolled. Expulsion occurred in 32 (53.3%) of 60 patients in Group-A and 51 (85.0%) of 60 patients in Group-B. Statistical analysis showed a significantly higher stone expulsion rate in Group-B compared with Group-A (
p <0.05) which is more or less similar to the study conducted by Cervenakov et al
14 where stone expulsion rate was 62.8% in standard treatment group and 80.4% in group where standard treatment was supplemented by Tamsulosin. Similarly, study conducted by Yilmaz E et al
12 Tamsulosin group showed 79.31% stone expulsion in comparison to 53.57% stone expulsion in group without Tamsulosin. A meta-analysis done by Lu Zet al
17 worked on twenty-nine trials with a total of 2,763 patients. The pooled analysis showed a19% improvement in stone clearance with tamsulosin. But Dellabella M et al
11 in a study showed stone expulsion rates were 100% and 70% in group treated with and without Tamsulosin respectively, These high rates of stone expulsion might be due to use of steroid (Deflazacort) in both groups.
In this study, effect of stone size on expulsion rate was observed. In smaller stones (3-5mm range), Group-A and Group-B included 19 and 18 patients respectively. Expulsion occurred in 9 (47.36%) patients of Group-A and 9 (50%) patients of Group-B; difference was not statistically significant (
p >0.05) but in relation to larger stones (6-8mm range), expulsion seen in 23 (56.09%) patients of Group-A and 42 (100%) patients of Group-B, difference was significant (
p < 0.05). A systematic review by Somani BK et al
15 claimed a result similar to our finding. But Dellabella M et al
11 in their study did not find any correlation between stone size and expulsion rate of stone.
In this study, complications like urinary tract infection, repeated colicky pain were encountered during study period. Urinary tract infection was encountered in 12(20%) patients of Group-A and 2(3.33%) patients of Group-B during four weeks therapy and was treated by appropriate antibiotics. Difference is statistically significant (
p <0.05). Above findings correlate with different studies conducted by Cervenakov et al,
14 Dellabella et al11 and Yilmaz E et al.
12 No serious side effects of Tamsulosin were encountered in any patients of either group, which could require the cessation of the medication or need for dose titration. Ten patients of Group-A and 8 patients of Group-B complained of mild headache and palpitation. In studies conducted by Dellabella et al and Porpiglia et al to enable spontaneous passage of distal ureteral stones, steroids have generally been included in medical treatment. However, in this study no steroid was used. The steroid sparing approach was another important feature of this study.
Conclusion:
Tamsulosin has a potentially important role for conservative expulsive therapy of juxtavesical ureteral stones, broadening pharmacological indications rather than endoscopic treatments for the resolution of this disease. Considering the findings of the present study and the studies previously done by others, it may be concluded that Tamsulosin supplemented conventional therapy is more effective than conventional hydrotherapy alone in the management of juxtavesical ureteral stones. Further studies are recommended to validate the promising and statistically significant results of this study.
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