Optimal duration of medical expulsive therapy for lower ureteral stones: a critical evaluation.

To evaluate the optimal duration of Medical Expulsive Therapy (MET) application for distal ureteric stones on a time period based manner. 89 patients with 5-10 mm distal ureter stones received tamsulosin (0.4 mg) for MET and diclofenac sodium (75 mg) for analgesia. Patients were evaluated once a week for 4 weeks. Radiologic stone passage was evaluated by kidney ureter bladder (KUB) and ultasonography where non-contrast computed tomography (NCCT) was also performed if needed. While 23 cases (28.4%) were SF after first week, 23 were SF (28.4%) after 2 weeks, 9 cases (11.1%) after 3 and lastly 7 cases (8.6%) became SF after four weeks. Nineteen (23.5%) cases were not SF after 4 weeks. A positive relationship was found between the time period elapsed for stone passage and ureteral wall thickness (UWT) along with the degree of hydronephrosis. In addition, mean number of renal colics and emergency department (ED) visits were found to be higher in patients passing stones in the 4th week along with the ones who could not despite MET. SFR for distal ureteric stones sizing 5-10 mm was higher within the first 3 weeks under MET application. Thus, waiting for a longer period of time may result in increased analgesic and unnecessary MET treatment with increased risk of emergency department visits and additional costs as well. We believe that other options could be considered in such cases who are not SF at the end of the first 3 weeks.

Deciding on a novel predictive value to gauge how well patients with lower ureteric stones respond to medical expulsive therapy.

This study, conducted over 4 years in Baghdad, Iraq, aimed to determine the importance of ureteric jet assessment in medical expulsive therapy (MET) for distal ureteral stones. A total of 156 patients with distal ureteral stones (≤ 10 mm) participated, and their ureteric jets were observed using a color Doppler scanner before and after 2 weeks of MET. The main focus was the success rate of stone expulsion. Our results showed that 50% of patients had detectable ureteric jets after 2 weeks of MET, and 21.8% experienced successful stone expulsion. After 4 weeks, 23.7% achieved stone expulsion, while 54.5% still had remaining stones. Patients who had a positive baseline ureteric jet were significantly more likely to successfully expel their stones. This study highlights the importance of monitoring ureteric jet movement in MET for distal ureteral stones.

Improved stone quality of life in patients with an obstructing ureteral stone on alpha-blocker medical expulsive therapy.

PURPOSE: Though controversial, alpha blockers are used widely for ureteral stone passage. However, its effects on the patient-reported Quality of life (QOL) is unknown. We compared the QoL of patients on alpha-blocker medical expulsive therapy (MET) to patients not on MET (noMET) utilizing the validated Wisconsin Stone Quality of Life (WISQOL). METHODS: This prospective study included patients prescribed either MET or noMET after presentation with symptomatic, obstructing ureteral stones. The treatment arm was decided at the point of care by the initial treating physician and included analgesia and antiemetics. Tamsulosin (0.4 mg daily) was prescribed for the MET group. The WISQOL survey was administered at baseline, 7-, 14-, 21- and 28-days following discharge from the ED or until stone expulsion. RESULTS: 197 patients were enrolled, of which 116 (59.2%) completed questionnaires for analysis, 91 in the MET group and 25 in noMET. Average ureteral stone size was 4.7 mm (SD 1.8) and 3.1 mm (SD 1.0) for MET and noMET, respectively. Of completed surveys, 105 (90%) were completed at day 7, 67 (57.6%) at day 14, 53 (45.7%) at day 21, and 40 (34.5%) at day 28. MET was associated with improved QoL scores across all WISQOL domains compared to noMET. Stone size, age, race, sex, comorbidity score and a prior stone history were not associated with reduced QoL. CONCLUSIONS: The use of MET was associated with improved QOL on all WISQOL metrics compared to noMET patients. Improved stone QOL may be an indication of alpha-blocker therapy in patients with ureteral stone colic.

Evaluation of the efficacy and safety of either or both mirabegron and silodosin, as a medical expulsive therapy for distal ureteric stones.

OBJECTIVE: To evaluate efficacy and safety of either or both silodosin and mirabegron as MET for distal ureteric stones ≤ 10 mm. PATIENTS AND METHODS: This study enrolled a total of 105 patients, aged between 20 and 56 years, diagnosed by single radiopaque distal ureteral stone measuring ≤ 10 mm. The recruitment period spanned from May 2020 to December 2021. The patients were randomly divided into three groups, with each group consisting of 35 participants. Group A received a once-daily dose of 8 mg of silodosin, group B received a once-daily dose of 50 mg of mirabegron, and group C received a combination of both medications. Treatment was administered to all patients until the stone was expelled or for a maximum duration of four weeks. The stone-free rate was determined by analyzing KUB films with or without ultrasonography. RESULTS: The rate of stone expulsion was significantly higher in group C compared to groups A and B (P = 0.04 and P = 0.004, respectively). The mean (standard deviation) time for stone expulsion in groups A, B, and C was 14 ± 2.3 days, 11 ± 3.1 days, and 7 ± 2.2 days, respectively. Group C demonstrated a significantly shorter stone expulsion time compared to groups A and B (P = 0.001 and P = 0.04, respectively). The frequency of renal colic in group C was significantly lower than that in groups A and B, resulting in a reduced requirement for analgesics (P < 0.05). Anejaculation occurred at a significantly higher rate in the silodosin group (73.9%) and combination group (84%) compared to the mirabegron group (P < 0.05). CONCLUSIONS: The findings of this study suggest that both silodosin and mirabegron are effective treatments for the expulsion of lower ureteric stones. Furthermore, the combination of these medications leads to an increased rate of stone expulsion and a reduced duration of expulsion.

Development of a new scoring system predicting medical expulsive therapy success on 4-10 mm distal ureteral stones: medical expulsive therapy stone score (METSS).

Ureteral stone passage by using medical expulsive therapy (MET) are affected by numerous radiological and clinical parameters. We aimed to construct a scoring system, which would be based on clinical and computed tomography (CT)-derived data, to predict the success of the MET approach. 186 patients presenting to urology clinic or emergency department with unilateral single 4-10 mm distal ureteral stone and who had MET were included. All patients were divided into two groups as the MET-successful group and the MET-unsuccessful group. The success rate of MET was 67.2%. Stone size ≥ 6.5 mm, stone density > 1078 HU, ureteral wall thickness (UWT) > 2.31 mm, ureteral diameter (UD) > 9.24 mm, presence of periureteral stranding (PUS) and presence of diabetes mellitus (DM) were stated as the independent risk factors. Based on the regression coefficients on multivariate logistic regression analysis, 1 point for stone size > 6.5 mm, 2 points for stone density > 1078 HU, 2 points for UWT > 2.31 mm, 3 points for UD > 9.24 mm, 1 point for presence of PUS and 1 point for presence of DM were assigned to patients for each risk factor. Higher medical expulsive therapy stone score (METSS) indicated lower MET success. All patients were classified into three risk groups according to METSS: low risk (0-3 points; success percentage: 92.8%); intermediate risk (4-5 points; success percentage: 60.4%) and high risk (6-10 points; success percentage: 8.3%). The METSS seems to separate successfully the patients with a favorable or adverse constellation of factors.

Tamsulosin vs. Tadalafil as medical expulsive therapy for distal ureteral stones: a systematic review and meta-analysis.

PURPOSE: Medical expulsive therapy (MET) is recommended for distal ureteral stones from 5 to 10 mm. The best drug for MET is still uncertain. In this review, we aim to compare the effectiveness of tadalafil and tamsulosin for distal ureteral stones from 5 to 10 mm in terms of stone expulsion rate (SER), stone expulsion time (SET) and the side effect profile. MATERIALS AND METHODS: A comprehensive literature search was conducted on MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Scopus and Web of Science, from inception until April 2023. Only randomized controlled trials were included in the analysis. RESULTS: Eleven publications with 1,330 patients were included. We observed that tadalafil has a higher SER (OR 0.55, CI 95% 0.38;0.80, p=0.02, I2=52%) and the same efficacy in SET (MD 1.07, CI 95% -0.25; 2.39, p=0.11, I2=84%). No differences were found when comparing side effects as headache, backache, dizziness, and orthostatic hypotension. CONCLUSION: Tadalafil has a higher stone expulsion rate than tamsulosin as a medical expulsive therapy for patients with distal stones from 5 to 10 mm without differences in side effects.

Effectiveness of prophylactic antimicrobial levofloxacin against postureteroscopic lithotripsy infection: A multicenter prospective open-label randomized controlled trial.

BACKGROUND: To verify the appropriate prophylactic agent to prevent ureteroscopic lithotripsy infection, which is safe, effective, convenient, reasonable, and with best pharmacoeconomic benefit ratio, to provide evidence for clinical practice. METHODS: This study is a multicenter, open-label, randomized, positive drug-controlled trial design. From January 2019 to December 2021, patients with ureteral calculi who were going to undergo retrograde flexible ureteroscopic lithotripsy were selected from urology departments in 5 research centers. The patients enrolled were randomly divided into the experimental group and the control group according to the random number table by blocking randomization. In the experimental group (Group A), 0.5 g levofloxacin was given 2 to 4 hours before surgery. In the control group (Group B), cephalosporin was injected 30 minutes before surgery. The infectious complications, the incidence of adverse drug reactions and the economic benefit ratio were compared between the 2 groups. RESULTS: A total of 234 cases were enrolled. There was no statistically significant difference between the 2 groups at baseline. Postoperative infection complications were 1.8% in the experimental group, which was significantly lower than 11.2% in control group. The type of infection complication in both groups was asymptomatic bacteriuria. The cost of drugs in the experimental group was 19.89 ± 13.11 yuan, which was significantly lower than cost of drugs in the control group of 41.75 ± 30.12 yuan. The levofloxacin application had favorable cost-effectiveness ratio. The difference in safety between 2 groups was not significant. CONCLUSION: The application of levofloxacin is safe, effective, and low-cost regimen for postureteroscopic lithotripsy infection prevention.

A prospective evaluation of patient-reported outcomes during follow-up of ureteral stones managed with medical expulsive treatment (MET).

Patient-reported outcomes (PROs) for ureteral stones predominantly assess the pain. Despite the lack of evidence, multiple trials studying the efficacy of medical expulsive therapy (MET) have used PROs to define spontaneous stone passage (SSP). We aim to objectively evaluate the accuracy of PROs to predict successful SSP and the probability of patient's symptom resolution after stone passage. A single-center, prospective observational study recruiting adults with isolated, uncomplicated, ≤ 10 mm ureteral calculus was conducted. All patients received 4 weeks of MET, and SSP was confirmed by low-dose non-contrast-enhanced computed tomography (NCCT). The accuracy of PROs: "pain cessation," "decreased pain," "stone seen," and "stone capture" to predict successful SSP were evaluated in 1 month. The patient's symptom resolution rate was assessed at 1 and 4-month follow-ups. A total of 171 patients were included, and the overall SSP rate was 66.4% (n = 99). Patient-reported pain cessation, stone visualization, and stone capture were associated with successful SSP, but their accuracy was 59, 53, and 43%, respectively. Moreover, 25% of patients reporting complete pain cessation still harbored ureteral calculus. Pain resolved in 91% of patients after SSP at a 4-month follow-up. While hematuria and nausea resolved in all patients, lower urinary tract symptoms (LUTS) were not resolved in 17% of patients. We concluded that patient-reported pain cessation, stone visualization, and stone capture predict successful SSP, but confirmatory imaging is required due to the poor accuracy of these measures. The significant rates of non-pain-related symptoms indicate their significant contribution to patient morbidity. Clinical Trial Registration: Registered in Clinical Trial Registry of India (CTRI), Registration number: CTRI/2020/10/028777 (29th October 2020).

A Comparison of Boron Supplement and Tamsulosin as Medical Expulsive Therapy for Urinary Stones After Extracorporeal Shock Wave Lithotripsy: a Randomized Controlled Clinical Trial.

Treatment with alpha-blockers has been used in many studies to facilitate stone clearance after extra-corporeal shock wave lithotripsy (ESWL), based on mediating ureteral wall relaxation. Ureteral wall edema is another barrier against the stone passage. We aimed to compare the effectiveness of boron supplement (due to its anti-inflammatory effect) and tamsulosin in the passage of stone fragments after ESWL. Eligible patients after ESWL were randomly assigned to two groups and were treated with boron supplement (10 mg/BD) or tamsulosin (0.4 mg per night) for 2 weeks. The primary outcome was the stone expulsion rate according to the remained fragmented stone burden. The secondary outcomes were the time of stone clearance, pain intensity, drug side effects, and the need for auxiliary procedures. In this randomized control trial, 200 eligible patients were treated with boron supplement or tamsulosin. Finally, 89 and 81 patients in the two groups completed the study, respectively. The expulsion rate was 46.6% in the boron and 38.7% in the tamsulosin group, which there was no statistically significant difference between the two groups (p = 0.003), as well as the time of stone clearance (7.47 ± 22.4 vs 6.52 ± 18.45, days, p = 0.648, respectively), after 2-week follow-up. Moreover, pain intensity was the same in both groups. No Significant side effects were reported in the two groups. Boron supplement could be effective as adjuvant medical expulsive therapy after ESWL with no significant side effects in short-term follow-up. Iranian Clinical Trial Registration number and date of registration: IRCT20191026045244N3, 07/29/2020.

The Effect of Preoperative Tamsulosin on Ureteral Navigation, Operation, and Safety: A Systematic Review and Meta-Analysis.

INTRODUCTION: Urolithiasis is one of the most common diseases in the world, and at present, ureteroscopy (URS) is the first choice for its treatment. Although the effect is good, there is a risk of insertion failure of ureteroscope. Tamsulosin, as an α-receptor blocker, has the function of relaxing ureteral muscles, and can help stones to be discharged from ureteral orifice. In this study, we aimed to determine the effect of preoperative tamsulosin on ureteral navigation, operation, and safety. METHODS: This study was conducted and reported according to the meta-analysis extension of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The PubMed and Embase databases were searched for studies. Data were extracted according to the PRISMA principles. We collected and combined randomized controlled trial and researches in reviews of preoperative tamsulosin to explore the effect of preoperative tamsulosin on ureteral navigation, operation, and safety. A data synthesis was performed using RevMan 5.4.1 software (Cochrane). Heterogeneity was mainly evaluated with I2 tests. Key metrics include: success rate of ureteral navigation, time of URS, stone-free rate, and postoperative symptoms. RESULT: We summarized and analyzed 6 studies. We noted a statistically significant improvement in the success rate of ureteral navigation (Mantel-Haenszel [M-H], odds ratio [OR]: 3.78, 95% confidence interval [CI]: [2.34, 6.12], p < 0.01) and stone-free rate (M-H, OR: 2.25, 95% CI: [1.16, 4.36], p = 0.02) with tamsulosin preoperatively. At the same time, we also observed that postoperative fever (M-H, OR: 0.37, 95% CI: [0.16, 0.89], p = 0.03) and postoperative analgesia (M-H, OR: 0.21, 95% CI: [0.05, 0.92], p = 0.04) were also reduced because of preoperative tamsulosin. CONCLUSION: Preoperative tamsulosin can not only increase the one-time success rate of ureteral navigation and the stone-free rate of URS but also reduce the incidence of postoperative adverse symptoms such as postoperative fever and postoperative pain.

Obstructing Ureteral Calculi and Presumed Infection: Impact of Antimicrobial Duration and Time From Decompression to Stone Treatment in Developing Urosepsis.

OBJECTIVE: To determine whether the duration of antibiotic treatment and timing between urgent renal decompression and stone intervention impacts the risk of developing urosepsis following definitive stone treatment. MATERIALS & METHODS: A retrospective review of patients who were diagnosed with obstructive urolithiasis and underwent urgent decompression with a ureteral double J stent or percutaneous nephrostomy at our institution between 2012 and 2018 was performed. We narrowed our analysis to the subset of patients who had suspected infection and received definitive stone treatment at our institution. Demographic, infection and antimicrobial data, and initial admission to stone treatment characteristics were collected. Factors associated with developing urosepsis were analyzed. RESULTS: We identified 872 patients who were treated with urgent renal decompression, of which 215 were analyzed that had suspected infection and also received definitive stone removal at our institution. Thirty-three had fevers, 64.2% had a positive urine culture, and 45.6% had urosepsis at the initial presentation. The median antibiotics duration post decompression was 13 days (IQR 8-18). The median duration from decompression to stone treatment was 17 days (IQR 12-27). Of all, 4.6% of the patients developed urosepsis post ureteroscopy and 5% post percutaneous nephrolithotomy. No factors were associated with developing urosepsis post stone treatment on logistic regression analyses. CONCLUSION: In patients requiring urgent decompression for obstructing urolithiasis and suspected infection, the time between decompression and stone treatment and the length of antibiotic exposure did not impact rates of postoperative urosepsis. This highlights the importance of maintaining high clinical suspicion for prolonged use of antibiotics, to prevent overtreatment and possible exacerbation of antibiotic resistance.

Efficacy Of Alpha-Adrenergic Receptor Antagonists In The Treatment Of Distal Ureteric Stones: A Paediatric Study.

BACKGROUND: European association of urology (EAU) recommended α- blockers for managing distal ureteric stones in the paediatric population. This paper will help to understand the efficacy of Silodosin as a medical expulsive agent for distal ureteric stones in children, along with the required time duration of stone expulsion. METHODS: Forty participants were enrolled and evaluated for complaints, pain severity, associated symptoms, and ultrasound was done to confirm the position and size of the distal stone. Follow-ups were scheduled after every 7 days (1 week) for redo ultrasound and assessment of the stone position. Data was entered and analyzed in the SPSS version 23. To evaluate the significance of data chi-square test was performed, p-value <0.005 was considered significant. RESULTS: The minimum and maximum age limits recorded are 3 years and 18 years respectively with a mean age of 9.5±4.5 years and mean stone size was measured as 0.6±0.1 cm. Distribution of stone size indicated the minimum size of 0.4 cm and maximum of 1.0 cm stone in study subjects. Maximum stone expulsion was reported within 14 days or an initial 2 follow-up scans. CONCLUSIONS: The efficacy of Silodosin and medical expulsive therapy evaluated the effect on pain management as pain episodes declined with Silodosin treatment and spontaneous passage of stones were increased within the first 14 days of treatment. This study will be a beneficial contribution in literature especially in a developing country population where paediatric urolithiasis is on expansion and ongoing.

Silodosin versus Tamsulosin for Medical Expulsive Therapy of Ureteral Stones: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background and Objectives: This systematic review and meta-analysis of randomized controlled trials was performed to compare the therapeutic effects and safety profiles of silodosin and tamsulosin for medical expulsive therapy (MET) of ureteral stones. Materials and Methods: We searched PubMed, EMBASE, the Cochrane Library, and Web of Science to identify articles published before July 2022 that described randomized controlled trials comparing silodosin and tamsulosin for MET of ureteral stones. Endpoints were stone expulsion rate, stone expulsion time, and total complication rate. Results: In total, 14 studies were included in our analysis. The size of ureteral stones was <1 cm. Compared with tamsulosin, silodosin resulted in a significantly higher stone expulsion rate (p < 0.01, odds ratio (OR) = 2.42, 95% confidence interval (CI) = 1.91 to 3.06, I2 = 0%) and significantly shorter stone expulsion time (p < 0.01, mean difference = −3.04, 95% CI = −4.46 to −1.63, I2 = 89%). The total complication rate did not significantly differ between silodosin and tamsulosin (p = 0.33, OR = 1.15, 95% CI = 0.87 to 1.52, I2 = 7%). Conclusions: Compared with tamsulosin, silodosin resulted in significantly better expulsion of ureteral stones <1 cm. The total complication rate did not significantly differ between silodosin and tamsulosin. Thus, silodosin may be superior to tamsulosin for MET of ureter stones <1 cm.

The Efficacy of Mirabegron in Medical Expulsive Therapy for Ureteral Stones: A Systematic Review and Meta-Analysis.

Background: This study aimed to assess the efficacy of mirabegron (50 mg daily) as a medical expulsive therapy for ureteral stones in adults. Materials and Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science from inception to July 2021 to collect the clinical trials. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies by using the Cochrane risk of bias tool. Review Manager 5.3 software was used for the meta-analysis. Results: A total of four studies were included, involving 398 patients: 197 patients in mirabegron group and 201 patients in control group. The meta-analysis showed that the stone expulsion rate was higher in the mirabegron group than in the control group (OR: 2.12; 95% CI: 1.33 to 3.40; p=0.002). Subgroup analysis identified that the stone expulsion rate of patients with stone size <5/6 mm was significantly higher than that of patients with stone size ≥5/6 mm (OR: 0.31; 95% CI: 0.13 to 0.72; p=0.006). But no significant difference was identified between the mirabegron group and the control group for the stone expulsion interval (MD: -1.16, 95% CI: -3.56 to 1.24; p=0.35). In terms of pain episodes, the mirabegron group was significantly lower than that of the control group (MD: -0.34, 95% CI: -0.50 to 0.19; p < 0.0001). Conclusions: The medical expulsive therapy with mirabegron had a significant effect in improving the stone expulsion rate for patients with ureteral stones, especially in those whose stone size <5/6 mm. Mirabegron had no effect on the stone expulsion interval but did decrease the pain episodes.

A randomized trial of adjuvant tamsulosin as a medical expulsive therapy for renal stones after shock wave lithotripsy.

Adjuvant medical expulsive therapy (MET) for shock wave lithotripsy (SWL) is controversial. With limited use of the computed tomography (CT), the stone free rate (SFR) become overestimated. Herein we evaluate tamsulosin post-SWL for renal stone using the CT to assess SFR. A randomized controlled trial (NCT05032287) was carried out for renal stone patients amenable for SWL. Patients were allocated after 1st session of SWL to receive tamsulosin 0.4 mg or placebo once daily from the 1st day of SWL and for 3-months or becoming stone free. The primary outcome was SFR, defined by presence of residual fragments (RF) ≤ 3 mm (3C-SFR). The 3C-SFR were 73.8% and 59.6% in tamsulosin and placebo groups, respectively (p = 0.03). The median (IQR) pain scores were 3 (3, 5) and 5 (3, 6) in tamsulosin and placebo groups, respectively (p = 0.04), However, the post-SWL complication and add-on analgesia needed showed no significance differences between groups. The median time for stone free were 30 days (95% CI: 27.29-32.71) in tamsulosin arm, and 36 days (95% CI: 31.01-40.99) in placebo arm, HR = 1.42 (95% CI: 1.02-1.98). Tamsulosin has more reversible adverse effect, compared to placebo (p = 0.03). In our study, the use of tamsulosin as MET following SWL facilitates expulsion of retained residual fragments. Tamsulosin shortens time to reach stone free, decreases pain scores. However, tamsulosin does not affect the add-on IV analgesics and have more reversible adverse effect, compared to placebo.

The Efficacy of Sexual Intercourse Or Masturbation For The Expulsion Of Distal Ureteral Stones In Men: A Systematic Review And Meta-analysis Of Randomized-controlled Trials.

PURPOSE: Several randomized-controlled trials (RCTs) were performed to compare the efficacy of sexual intercourse or masturbation and no sexual activity in treating distal ureteral stones, indicating conflicting results. The meta-analysis was conducted to assess the role of sexual intercourse or masturbation in the treatment of distal ureteral calculi. MATERIALS AND METHODS: PubMed, Cochrane Library, EMBASE, Scopus, Clinicaltrail.gov, and Web of Science were searched by October 2021. Men who were instructed of no sexual intercourse or masturbation, and only received standard symptomatic treatment are comparators. Relative risk (RR), weighted mean difference (WMD), and their 95% confidence intervals (CIs) were calculated using random or fixed effects models. RESULTS: Five RCTs including 500 subjects were analyzed in the study. Compared with controls, subjects in experimental group had significantly higher expulsion rate at 2nd and 4th week (95%CI: 1.334 to 2.638, RR: 1.876, I2 = 73.6%, P < .001; 95%CI: 1.148 to 1.752, RR: 1.418, I2 = 55.9%, P < .001), significantly decreased requirement for analgesic injections (95%CI: -1.071 to -.126, WMD: -.598, I2 = 90.3%, P = .013), and significantly shorter expulsion time (95%CI: -6.941 to -.436, WMD: -3.689, I2 = 83.7%, P = .026). CONCLUSION: Performing sexual intercourse or masturbation 3 or 4 times a week can be an alternative treatment option of distal ureteral calculi (0-10 mm in size). However, more clinical evidence with better designs solving raised concerns is warranted.

Efficacy of Mirabegron as Medical Expulsive Therapy for Distal Ureteral Stones: A Prospective, Randomized, Double-Blinded, Controlled Study.

BACKGROUND: Today, medical expulsive therapy (MET) is more effective and commonly used in distal ureteral stones when compared with conservative treatments. Many treatments, namely, alpha-adrenergic blockers and calcium channel blockers, prostaglandin synthesis inhibitors, glyceryl trinitrate, and steroids, have been, therefore, utilized to mitigate such complications and accelerate stone expulsion. Several animal and human studies revealed the presence of ß3-receptors in the ureter and bladder, where stimulating these receptors could relax the distal ureteral segment. OBJECTIVES: The aim of the study was to evaluate the efficacy of use of mirabegron as MET for distal ureteral stones (intramural and extramural). METHODS: This is a prospective randomized controlled study including 90 patients who had distal ureteral stones less than 10 mm and were evaluated between January and June 2020. The patients were classified into 3 groups: group (A) 30 patients: mirabegron 50 mg d-1 + diclofenac Na 100 mg tab (to be taken only during colic episodes), group (B) 30 patients: tamsulosin HCL 0.4 mg cap + diclofenac Na 100 mg tab (to be taken only during colic episodes), and group (C) 30 patients: diclofenac Na 100 mg tab only (to be taken only during colic episodes). Age, sex, stone size, laterality, and grade of ureterohydronephrosis were recorded. Patients were observed for 30 days, and ureteroscopy was completed for those with nonexpulsed stones. Follow-up parameters included number of renal colic episodes, duration of medical therapy, stone expulsion time, and stone expulsion rate (SER). RESULTS: In the group (A), 2 (6.6%) patients were excluded due to nasal congestion, and 1 (3.3%) patient was excluded due to a 20-mm Hg systolic blood pressure increase. Four (13.3%) patients in group (B) were noncompliant on medical treatment. In addition, 2 (6.6%) patients in group (A), 1 (3.3%) patient in group (B), and 5 (16.6%) patients in group (C) who did not attend follow-up examinations were excluded from the study. The SER increased significantly in group (A) and (B) when compared with group (C). The mean time of stone expulsion was about 15, 25, and 12 days for groups A, B, and C, respectively, and there was a significant statistical difference (p value = 0.006) among the 3 groups. The mean number of renal colic episodes of group (A) of patients was 1.8 times, while that of group (B) was 2.6 times and that of group (C) was 2.16 times with no significant statistical difference after comparing the 3 groups (p value = 0.660). CONCLUSIONS: Treatment with mirabegron appears to be a safe and effective medical expulsion therapy for distal ureteric stones and is better than tamsulosin.

Current and emerging pharmacological targets for medical expulsive therapy.

The primary goals of medical expulsive therapy are to increase the rate of stone expulsion along the ureter to avoid ureteral obstruction and reduce ureteral colic and thus avoid the need for surgical and more invasive interventions. This review focussed on the findings from in vivo and in vitro animal and human studies that have investigated the pharmacological mechanisms controlling ureteral motility and their translation to current and potentially new clinically used drugs for increasing the rate of stone expulsion along the ureter. The complicated contractility profile of the ureter, which alters with age, tissue segment region, orientation and species contributes to the difficulty of interpreting studies on ureteral pharmacology, which translates to the complexity of discovering ideal drug targets for medical expulsive therapy. Nevertheless, the current drug classes clinically used for patients with stone lodgement include α1 -adrenoceptor antagonists, calcium channel blockers and NSAIDS, whilst there are promising targets for drug development that require further clinical investigations including the phosphodiesterase type 5 enzyme, ß-adrenoceptors and 5-HT receptors.