ABSTRACT
Purpose:
A ureter diameter exceeding 6 mm is termed megaureter. This study aimed to evaluate the clinical features of primary non-refluxing megaureter (PNMU) and the importance of ureteral diameter in its management.
Methods:
Clinical, radiological, and operative findings and long-term outcomes of PNMU followed or operated on between 2011 and 2023 were evaluated retrospectively. Patients with vesicoureteral reflux, a history of lower urinary tract pathology or surgery, and a follow-up <18 months were excluded.
Results:
Among 32 patients (12.5% female, 87.5% male), 50% were diagnosed prenatally. Twenty-six patients had unilateral, six had bilateral megaureters. Over a mean follow-up of 94.3 ± 53.4 months, 37.5% were managed conservatively, 62.5% required intervention. Nine underwent open surgery, 11 underwent double-J-stenting. Median operation age was comparable between surgical groups (P > 0.05) but significantly lower in patients with urinary tract infection (P: 0.007). Ureteral diameter decreased from 10.4 mm (range: 6.2–24.2) to 6.9 mm (range: 0–17) in conservatively managed cases, from 11 mm (range: 8–24.2) to 9 mm (range: 0–19) in double-J-stent group, and from 9.7 mm (range: 6.2–18.8) to 4.3 mm (range: 0–13) in the open surgery group (P > 0.05). No significant difference was observed among the peak measured ureter diameters in the conservatively managed group (median: 12 mm, range: 9–33), preoperative ureter diameters in the double-J-stent group (median: 12.5 mm, range: 8.8–17), and open surgery group (median: 14 mm, range: 8–31) (P > 0.05).
Conclusion:
Ureteral diameter has limited importance in PNMU management. Conservative management may be an option even in advanced dilatations. Postoperative ureteral dilatation may persist at varying levels and durations.
KEYWORDS: Congenital megaureter, nonrefluxing, pediatrics, ureteral diameter
INTRODUCTION
Ureter diameter exceeding 6 mm is termed a megaureter. Megaureters are classified based on the international system proposed by Smith in 1977 as refluxing, obstructed, both, or neither.[1] It can be primary or secondary due to extrinsic causes. When a congenital megaureter is primary and not related to vesicoureteral reflux (VUR), it is named a primary nonrefluxing megaureter (PNMU). Some of these patients have an adynamic or stenotic ureteral segment, which causes obstruction and results in PNMU.[2]
Before widespread use of prenatal screening, most of the megaureter patients were presenting with febrile urinary tract infection (UTI) and renal scarring, and most of them required surgery. Diagnosis of megaureter has become easier with the development of prenatal screening. Some prenatally diagnosed cases have shown spontaneous resolution, particularly during the first 2 years of life. Conservative treatment has gained popularity in the last decades due to this observation.[3,4,5] While spontaneous resolution is common, febrile UTI, increasing dilatation, or renal damage may also occur. Treatment of PNMU can be operative or nonoperative according to the cause of dilatation and clinical presentation. Recurrent UTIs, decreased renal function, progressive renal scarring, and increasing dilatation usually indicate the need for surgical intervention. Ureteral diameter was thought to be a reasonable predictor of resolution. There are different reports of different ureter diameters as a cutoff indicating surgical need, but consensus has not been established yet.[2,6,7] This study aimed to evaluate the clinical features of PNMU and the importance of ureteral diameter in its management.
METHODS
Patients who were managed and operated on by a single surgeon at a tertiary pediatric surgical center, registered with the International Classification of Diseases code of Q62.2 – Congenital Megaureter between 2011 and 2023, were extracted from the hospital records. Written informed consent was obtained from each patient. Patients were evaluated with ultrasonography at regular intervals (initially every 3–6 months in infancy and annually thereafter, depending on clinical stability). Ureteral diameter was measured at its most distal part on a transverse view of the bladder. Voiding cystourethrography (VCUG) was performed to exclude VUR or infravesical obstructions, such as posterior urethral valves. Tc-99m-mercaptoacetyltriglycine (99mTc-MAG3) dynamic renal scintigraphy was used to assess renal function and drainage. Patients with refluxing megaureter, history of disease or surgery which could affect lower urinary tract functions, and a follow-up duration <18 months were excluded. The remaining 32 PNMU patients (38 renal units) were included in the study. Patient-level variables were analyzed per patient, whereas ureteral characteristics were analyzed per renal unit. Clinical, radiological, and operative findings and long-term outcomes of PNMU patients who were followed or operated on were evaluated retrospectively.
In our protocol, all patients diagnosed with PNMU were initially managed conservatively. During follow-up, surgical intervention was planned for patients who developed indications for surgery. Surgical indications included breakthrough UTIs, progressive upper urinary tract dilatation (hydronephrosis with progression to The Society of Fetal Urology Grade 4), differential renal function <40%, and/or significant decreases in differential renal function of ≥5% along with a plateau-type obstructive renogram curve lasting longer than 40 min on Tc99mMag3 renal dynamic scintigraphy. The decision between double-J stenting and open surgery was based on patient age, severity of obstruction, presence of infection, and surgeon preference. Double-J stenting was generally used for younger infants, patients selected based on parental preference, or those requiring temporary decompression, whereas open surgery was reserved for persistent obstruction following double-J stenting, other failed minimally invasive management, or initial parental preference. Patients were divided into three main groups according to the treatment modality: conservatively managed group, double-J stent group, and open surgery group. Complete resolution was defined as having a stable ureteral diameter of <7 mm at the last follow-up.
Frequencies, percentages, mean, standard deviation, median, range, and interquartile ranges (IQR) were used for descriptive analysis. The distribution of the data was tested using Shapiro–Wilk test. Continuous variables with nonnormal distribution were analyzed using Mann–Whitney U or Kruskal–Wallis tests, whereas normally distributed variables were analyzed using Student’s t-test. Categorical variables were analyzed using Chi-square test. The results were evaluated at 95% confidence interval and P < 0.05 significance level. Microsoft Excel and Jamovi statistical software (The Jamovi Project, 2022, Version 2.3) were used for data analysis. Institutional ethical board approval was obtained for this study (20.03.2024-67).
RESULTS
Among the 32 patients included in the study, 28 (87.5%) were male and 4 (12.5%) female. Twenty-six patients (81.2%) had unilateral, and six (18.8%) had bilateral megaureter, with a total of 38 renal units included in the study. Of 26 unilateral megaureter patients, 19 (73.1%) were left-sided and 7 (26.9%) were right. Prenatal diagnosis was made in 50% of the patients (males n: 13, females n: 3). Diagnosis was either incidental (n: 9, 28.1%) or with history of UTI (n: 7, 21.9%) for those without prenatal diagnosis, the median age at presentation was 9 months (range: 1–108, IQR: 2–85.8). All patients underwent VCUG which revealed contralateral VUR in two patients. Among these, one patient was diagnosed with recurrent UTIs, whereas the other was asymptomatic and incidentally detected. All patients were evaluated with renal scintigraphy. The mean differential renal function for unilateral cases was 45.8% ±8.3% (range: 24%–58%).
Febrile UTI was observed in 43.8% (n: 14) of the patients. In patients with UTI, recommendations regarding perineal hygiene were given, especially to female patients, and circumcision was performed in all male patients. Among the 32 patients included, 24 (75%) received continuous antibiotic prophylaxis (CAP), and 8 (25%) did not. During a mean follow-up period of 94.3 ± 53.4 months, 12 (37.5%) patients (15 renal units) were managed conservatively, and 20 (62.5%) patients (23 renal units) required intervention. The mean follow-up period was 88.3 ± 60.4 months in patients who needed intervention and 100 ± 46.4 months in conservatively managed patients (P > 0.05, Student’s t-test). No statistically significant difference was observed between prenatally and postnatally diagnosed patients in terms of treatment modality (P > 0.05, Chi-square test). Of the patients who underwent intervention, 9 (45%) underwent open surgery (10 renal units), and 11 (55%) had double-J-stenting (13 renal units). The duration of stent placement varied depending on clinical response (min 3–ma × 10 months). In our cohort, 2 patients initially treated with stenting subsequently required surgical intervention. Of all patients, 6 (18.7%) had co-existing ureteropelvic junction obstruction and underwent pyeloplasty. The median operation age was 8 months (range: 1–120, IQR: 1–66) for open surgery and 7.5 months (range: 4–96, IQR: 5–22) for double-J-stenting (P > 0.05, Mann–Whitney U test). The median operation age of the patients who had UTI was found to be significantly younger than others (P: 0.007, 4.5 months [range: 1–72, IQR: 1.7–7.5] vs. 10 months [range: 5–120, IQR: 7.5–78], Mann–Whitney U test). Ureter diameter decreased from 10.4 mm (range: 6.2–24.2, IQR: 9–12.4) to 6.9 mm (range: 0–17, IQR: 0–12) in conservatively managed cases, from 11 mm (range: 8–24.2, IQR: 10.4–13.8) to 9 mm (range: 0–19, IQR: 2.63–14) in double-J-stent group, and from 9.7 mm (range: 6.2–18.8, IQR: 8–11) to 4.3 mm (range: 0–13, IQR: 0–10) in the open surgery group. No significant difference was observed among the groups in terms of initial and final ureteral diameters (P > 0.05, Kruskal–Wallis test). No significant difference was observed between the peak measured ureter diameters in the conservatively managed group (median: 12 mm, range: 9–33, IQR: 9.97–17), preoperative ureter diameters in double-J-stent group (median: 12.5 mm, range: 8.8–17, IQR: 12–14), and preoperative ureter diameters in open surgery group (median: 14 mm, range: 8–31, IQR: 10–16) (P > 0.05, Kruskal–Wallis test). Complete resolution of dilation was observed in 17 renal units (44.7%) at last follow-up, almost equally distributed between surgical (n: 9) and conservative groups (n: 8) (P > 0.05, Chi-square test). Baseline characteristics and outcomes according to treatment groups are summarized in Table 1.
Table 1.
Baseline characteristics and clinical outcomes of patients according to management strategy
| Variable | Conservative (n=12) | DJS (n=11) | Surgery (n=9) | P |
|---|---|---|---|---|
| Age at intervention (months), median (IQR) | - | 7.5 (5–22) | 8 (1–66) | >0.05 |
| Prenatal diagnosis (%) | 21.1 | 10.5 | 18.4 | >0.05 |
| Initial ureter diameter (mm), median (IQR) | 10.4 (9–12.4) | 11 (10.4–13.8) | 9.7 (8–11) | >0.05 |
| Final ureter diameter (mm), median (IQR) | 6.9 (0–12) | 9 (2.6–14) | 4.3 (0–10) | >0.05 |
| Peak/preoperative ureter diameter (mm), median (IQR) | 12 (9–17) | 12.5 (12–14) | 14 (10–16) | >0.05 |
| Complete resolution (n) | 8 | 4 | 5 | >0.05 |
IQR: Interquartile ranges, DJS: Double-J Stenting
DISCUSSION
The majority of our cases was male and left sided. It is a well-known fact that most PNMU patients are male; it affects the left side predominantly and can be bilateral in 25% of cases.[2,8] Among our patients, 18.8% had bilateral PNMU. Buder et al. reported a similar rate of bilateral PNMU, 20%.[9] Prenatal diagnosis rate (50%) was high, which is consistent with literature.[6] Diagnosis was either incidental (28.1%) or with a history of UTI (21.9%) for those without prenatal diagnosis. Similarly, Rubenwolf et al. reported diagnosis was made following UTI in 18% of patients.[4] The median age at presentation was 9 months (range: 1–108, IQR: 2–85.8) for those without prenatal diagnosis. This finding is consistent with the literature as Rohner et al. reported 75% of UTIs occur in the 1st year of life.[8]
Ultrasonography is the primary imaging tool for diagnosing and, especially, for following up patients with megaureter. In patients with megaureter, VCUG is recommended to determine the nature of the dilatation. The timing and indications for dynamic renal scintigraphy are still unclear. Rivetti et al. recommend performing it at 4–6 weeks of life to evaluate renal function in every patient with PNMU >10 mm.[2] In our study, all patients with PNMU were evaluated using dynamic renal scintigraphy.
In the literature, the incidence of febrile UTIs in patients with PNMU has been reported to range between 14% and 43%.[4,6,8] In our study, this incidence was slightly higher, approaching the upper limit. However, gender, circumcision status, and CAP use might affect the UTI rate.[10] In addition, this could be explained by selection bias in our cohort. As contralateral VUR was detected in only two patients, and one of them was asymptomatic, it was not considered a major contributing factor to the overall UTI rate.
According to the literature, in the postnatal management of PNMU, surgical interventions have been required in 25%–45% of these patients.[5,6,7] Our intervention rate was higher than those in previous series. The relatively high intervention rate (62.5%) in our cohort may be explained by referral bias, as our institution is a tertiary center. Ureteral reimplantation is the gold standard surgical treatment, but endoscopic dilatation, double-J stenting, or rarely cutaneous ureterostomy can also be used.[2] At the consensus meeting of the British Association of Pediatric Urologists in 2012, the majority chose ureteric reimplantation with or without tapering in babies over 1 year of age and listed the alternative options for under 1 year of age as double-J stenting, endoscopic balloon dilatation, endoureterotomy, and cutaneous ureterostomy.[11] The chosen procedure and age at operation may vary depending on patient characteristics and are consequently reported variably across different studies. Braga et al. reported a mean operation age as 18 ± 11 months for ureteral reimplantation with tapering (52%), side-to-side refluxing ureterocystostomy (32%), and distal cutaneous ureterostomy (16%) procedures they performed, which is older compared to our results.[7] Dekirmendjian and Braga reported a median operation age as 22 months (range: 3–32) for ureteral reimplantation with or without tapering, also older compared to our results.[6] Farrugia et al. reported median age at operation as 6 months (range: 1–10), whereas Castagnetti et al. reported it as 3 months. Both used stenting as the preferred method and reported younger median operation ages than ours.[12,13]
A combination of PNMU and ureteropelvic junction obstruction is rarely seen. Lee et al. reported that 15 of 58 (25.8%) patients with PNMU had coexisting ureteropelvic junction obstruction.[14] Of all our patients, 6 (18.7%) had co-existing ureteropelvic junction obstruction and underwent pyeloplasty.
Dekirmendjian and Braga found grade of hydronephrosis was not associated with spontaneous resolution, but ureteral diameter was and recommended to use ureteral dilatation instead of hydronephrosis grade to predict resolution.[6] They reported that dilatation over 13 mm is most likely require surgical intervention, whereas diameter <11 mm is a strong predictor for spontaneous resolution.[6] Braga et al. reported that the mean ureteral diameter in surgical patients before surgery was 17 mm compared to 12 mm in patients who did not require surgery (P < 0.01).[7] Ureteral diameters do not always increase continuously; rather, they fluctuate, showing periods of increase and decrease. Based on a series in which ureteral diameter is accepted as a surgical indication, our aim was to compare the peak diameter in the conservative group with the diameter at the time of surgical indication, which represents the peak ureteral diameter in those patients. In our study, no significant difference was observed in terms of initial and final ureteral diameters (P > 0.05) and the peak measured ureter diameters (P > 0.05) between the groups.
Rubenwolf et al. reported a complete resolution rate as 39%.[4] It is important to compare resolution criteria among studies, if defined, before comparing resolution rates. For example, Braga et al. reported 75% of complete resolution rate but defined PNMU resolution by having a sTable 10 mm or less anteroposterior diameter of the renal pelvis and/or hydronephrosis grade 2 or less, <8 mm ureteral dilatation.[7] We reported 44.7% of complete resolution, and our criteria were having stable, <7 mm ureteral diameter in the last follow-up.
This study has several limitations. Its single-center design, small sample size, and potential selection bias due to the predominance of surgically treated patients may negatively affect generalizability. This is a retrospectively designed study, and there are limitations inherent in such analyses. However, in this study, all patients were regularly followed up by a single surgeon using a standardized approach. Despite these limitations, our study provides valuable long-term follow-up data from a single-surgeon cohort with standardized evaluation.
CONCLUSION
In this cohort, no statistically significant association was identified between ureteral diameter and the need for intervention in PNMU. Conservative management may be an option even in advanced dilatations. Postoperative ureteral dilatation may persist at varying levels and durations. However, these findings should be interpreted with caution, given the retrospective design and limited sample size. Larger, prospective studies are required to better define the role of ureteral diameter in clinical decision-making.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
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