The Efficacy and Safety of Adjunctive Alpha-blocker Therapy Before Flexible Ureteroscopy in the Management of Upper Ureteric Stones in Pediatrics Group

The incidence of pediatric urolithiasis has risen dramatically over the past few decades, with a reported rate of 4% per year .There is controversy regarding the practice of routine prestenting and balloon dilation to gain ureteral access in children. The AUA guidelines recommend against the routine use of prestenting. Balloon dilation of the ureteral orifice carries the risk of ureteral perforation and ureteral stricture, due to tissue ischemia .There are three subtypes of alpha- 1 adrenoceptors (ARs) in the ureteric wall: alpha-1A, alpha-1B and alpha-1D. In the proximal ureter, the distribution of ARs was alpha-1D ≥alpha-1B >alpha-1A. In the distal and middle ureters, the distribution of ARs was alpha-1D > alpha-1A > alpha-1B . Tamsulosin acts on α1A and α1D receptors causing the relaxation of the ureteric wall, which consequently increases the urine bolus and intra-ureteral pressure above the stone and lowers intra-ureteral pressure below the stone by decreasing peristalsis in association with the decrease in basal and micturition pressure, even at the bladder neck; thus, it increases the chance of stone expulsion .The management of ureteric stones consists of observation, medical expulsive therapy (MET), shockwave lithotripsy (SWL), ureteroscopy, percutaneous nephrolithotomy or open and laparoscopic stone surgery, depending on the clinical situation .The presumed mechanism of action of alphablockers is the inhibition of smooth muscle contraction in the ureter, causing relaxation of the ureter smooth muscle and reducing the strength and frequency of peristalsis .Flexible ureteroscopy (FURS) has been applied in recent years to the treatment of urinary stones. FURS presents overt advantages over other techniques, including improved resolution and increased optical field, high stone-free rate, reduced risk of bleeding, limited surgical injury, good repeatability, and speedy recovery; in addition, further miniaturization is possible. In children and infants, who have a relatively high stone recurrence rate, FURS could be performed repeatedly. FURS and holmium laser lithotripsy in treating infants and children has been previously assessed in the literature; however, most reports were limited in sample size.

Aim of the study:To evaluate efficacy adjunctive alpha-blocker therapy before Flexible ureteroscopy in the management of Upper ureteric stones in children as regard facilitating ureteric orifice navigation, Ureteral Dilatation, intraoperative and postoperative Complication, patient satisfaction and stone free rate.

PATIENTS AND METHODS This was a prospective randomized control study that was conducted at tertiary care hospital between September 2022 till September 2024. The study was approved by the Research Ethics Committee (REC) of Ain Shams University Faculty of Medicine. A detailed written informed consent was secured from patients' parents included in the study before enrollment after explaining the benefits and risks of the medication and procedure.

Eligibility criteria We included all children aged between 5 and 18 years with upper ureteric stones. Patients excluded from the analysis were children with active urosepsis, ureteral stricture, bilateral ureteral stones, children with already stented ureter, Children with congenital anomalies e.g. solitary kidney, duplex system, ureterocele, Those with hypersensitivity to α-blockers and Known hypotensive or bradycardic patients.

Participants and group allocation A total of 80 patients were included and randomly allocated into two groups depending on simple one to one randomization utilizing a sealed envelope prepared by an independent third party to ensure unbiased distribution. Outcome assessors, and statisticians were blinded to the treatment to minimize bias.. Group A: 40 Children received Tamsulosin 0.4 mg capsule for 5 days prior to Flexible uretroscopy. Group B: 40 Children didn't receive Tamsulosin 0.4 mg capsule prior to Flexible uretroscopy.

Pre-treatment assessment and baseline investigations All patients underwent a thorough clinical history and physical examination. Detailed medical history and surgical history including any surgery of the urinary tract, DJ application and ESWL. Laboratory work up including complete blood count (CBC), kidney functions test, liver functions test, hepatitis markers, coagulation profile, completer urine analysis and urine culture with sensitivity. All patients were subjected to imaging studies including pelvi-abdominal ultrasound, plain X-ray of urinary tract and CTUT All patients performed KUB in the morning day of the operation.

Alpha Blocker (Tamsulosin) 0.4 mg/dl was given once daily before sleep for 5 days to Group A only. Patients received preoperative prophylactic antibiotic. All cases had been performed by the same standard approach for Flexible Uretroscopy

Flexible uretroscopy:

The procedures were performed under general anesthesia in frog leg or lithotomy position in all patients. we start with cystoscopy followed by guide-wire insertion up to the renal pelvis and retrograde pyelography. Ureteral dilation was performed by teflon dilators up to 8 fr Then, we attempt to advocate the 7.5 fr flexible ureteroscope over the guide wire under direct vision up to the stone level. In all cases, Stone disintegration was done using Holmium Laser System and 200-micron laser fiber in dusting mode. A double-J stent was placed at the end of the procedure. Urethral catheter was left at end of procedure. DJ stents was removed 2 - 4 weeks after the operation. If navigation of the ureteral orifice is unsuccessful, then a ureteral JJ stent is placed for 10-14 days before attempting a second URS.

Postoperative:

Postoperatively, all patient had CBC done a few hours after the procedure, monitored for vital signs and urine color. All patients were assessed for residual stone presence 3 weeks after procedure by CTUT. The intraoperative and postoperative complications (e.g. fever, hematuria…), stone-free rate, and hospital stay were were reported according to the modified Clavien grading system. The primary endpoint was defined as being able to engage the flexible ureteroscope in the ureteral orifice to be able to perform the intended procedure. The second endpoint are safety of tamsulosin, intraoperative and postoperative Complication.

Statistical Analysis Data were collected, revised, coded and entered to the Statistical Package for Social Science (IBM SPSS) version 20. The qualitative data were presented as number and percentages while quantitative data were presented as mean, standard deviations and ranges when their distribution found parametric.

The comparison between two groups with qualitative data were done by using Chi-square test and/or Fisher exact test was used instead of Chi-square test when the expected count in any cell was found less than 5. The comparison between two independent groups with quantitative data and parametric distribution was done by using Independent t-test.

The confidence interval was set to 95% and the margin of error accepted was set to 5%. So, the p-value was considered significant as the following: P> 0.05 = non significant (NS), P < 0.05 = significant (S) and P < 0.001 = highly significant (HS).