Keywords urethral stricture - calibration - uroflowmetry - hypospadias
Introduction
Urethral stricture is a common complication following hypospadias repairs, posing
significant management challenges and the risk of multiple reoperations.[1 ] Long-standing urethral strictures can lead to urinary retention, urinary tract infections,
bladder dysfunction, and in severe cases, renal damage. In a minority of pediatric
patients, urethral stricture may even result in erectile dysfunction.[2 ] Current diagnostic methods, such as retrograde urethrography and cystoscopy, are
considered the gold standard for diagnosing urethral strictures.[3 ]
[4 ] Urethral calibration is also a relatively straightforward method for diagnosing
strictures and can be performed on an outpatient basis.[5 ] Sometimes, these invasive procedures need to be done under anesthesia, and may cause
pain or other potential complications. Therefore, there is a need to explore noninvasive
methods to reduce postexamination complications, minimize pain, and improve examination
cooperation in pediatric patients.
Uroflowmetry records the volume of urine and the duration of micturition through electronic
devices, providing the maximum urinary flow rate (Qmax ) and the average urinary flow rate (Qave ).[6 ] It is the best noninvasive urodynamic examination for detecting lower urinary tract
obstruction.[7 ] However, the results of uroflowmetry do not always match the actual presence of
urethral stricture in some patients,[8 ]
[9 ] which limits its diagnostic utility in cases with suspicious urethral stricture.
In clinical practice, further invasive examinations are still needed to confirm the
presence of true urethral stricture in patients whose uroflowmetry suggests possible
stricture. Moreover, current evidence is insufficient to recommend a specific cutoff
value for Qmax or Qave to determine the appropriateness of treatment.
Low urinary flow rates are common after hypospadias repair, especially following tubularized
incised plate (TIP) urethroplasty. Previous studies and clinical experience suggest
that the diagnostic accuracy of uroflowmetry may vary between TIP and non-TIP patients.[10 ]
[11 ] TIP urethroplasty utilizes only the urethral plate, while non-TIP procedures may
involve the foreskin or other tissues. These differences and biological variations
between tissues may affect postoperative urination, urethral compliance, and scar
formation. Therefore, this study compares the diagnostic performance of uroflowmetry
for urethral stricture in TIP and non-TIP patients using urethral calibration as the
reference standard and explores the potential quantitative relationship between uroflowmetry
and urethral calibration.
Materials and Methods
Study Design
This study is a retrospective cohort study. Data were collected retrospectively from
consecutive patients who underwent primary hypospadias repairs at our center from
June 2016 to June 2023. Patients were divided into TIP and non-TIP groups based on
their primary surgical techniques. This study complied with all principles and regulations
of the Helsinki Declaration and was approved by the Ethics Committee of our hospital,
with the ethical number 2024-IRB-0262-P-01.
The inclusion criteria were as follows: (1) Primary hypospadias; (2) age <18 years;
(3) the non-TIP group included patients who underwent one-stage and staged Duckett,
Duckett + Duplay procedure, Onlay, and Mathieu procedures, and the TIP group consisted
of patients who only underwent TIP procedure; (4) the availability of both urethral
calibration data and uroflowmetry data within 1 month before calibration postoperatively;
(5) follow-up >12 months. Exclusion criteria were (1) uroflowmetry data with a voided
volume of less than 50 mL; (2) urethral dilation, cystoscopy, or catheterization were
performed within 1 month prior to uroflowmetry; and (3) patients with concomitant
posterior urethral valves or neurogenic bladder.
Surgical Techniques Nuances
The surgeries were all performed by doctors with more than 10 years of rich experience
in hypospadias surgery. The materials for urethroplasty vary considerably among different
hypospadias repair techniques. In the TIP or Duplay procedures, the native urethral
plate is used as the urethroplasty material. By contrast, the Duckett procedure utilizes
a vascular pedicled prepuce, and the Onlay or Mathieu procedures incorporate a combination
of the native urethral plate and the prepuce. The severity of hypospadias cases suitable
for different surgical techniques differs significantly. The one-stage or staged Duckett,
or Duckett + Duplay procedure, is generally indicated for proximal hypospadias or
those accompanied by severe chordee. Conversely, the TIP, Onlay, and Mathieu procedures
are commonly used for mid or distal hypospadias. Moreover, the development state of
the urethral plate plays a vital role in determining the appropriate surgical approach.
The TIP procedure relies on a well-developed urethral plate. In contrast, the Onlay
and Mathieu procedures show greater adaptability to cases with suboptimal urethral
plate development.
Calibration and Uroflowmetry
Calibration could be conducted on an outpatient basis without anesthesia when there
was a parental request or suspicion of urethral stricture. It could also be conducted
under anesthesia during surgeries for associated conditions not requiring urethral
reconstruction, such as prepuce epidermoid cysts, hydrocele, and undescended testes.
Urethral calibration was performed by surgeons experienced in hypospadias repairs.
The calibration value (C) was defined as the largest size of the urethral sound that
could be inserted without significant resistance, breakthrough feeling, or causing
noticeable pain for outpatients. The urethral stricture was defined as a calibration
value less than 8 Fr (<1 year), less than 10 Fr (1 year to prepuberty), and less than
12 Fr (postpuberty).[12 ]
[13 ] Uroflowmetry was performed by trained professionals using a uroflowmeter (Medical
Measurement Systems, the Netherlands) in patients without untreated postoperative
urethral fistulas or dehiscence. The assessment included Qmax , Qave , and Siroky nomogram intervals. Data were collected on demographic information, surgical
techniques, uroflowmetry results, urethral calibration outcomes, and postoperative
complications.
Sample Size
In this retrospective cohort study, participants were divided into two groups: the
urethral calibration group and the uroflowmetry group, with urethral stricture serving
as the primary outcome measure. The diagnostic difference between the two groups for
urethral stricture is 10%, with a standard deviation (SD) of uroflowmetry being 4.
Assuming a two-sided α of 0.05 (one-sided 0.025), a power of 0.9 (1 − β), and a noninferiority
margin of 4, and referring to the method by Hueber et al,[10 ] the calculated sample size for the urethral calibration group is 23 cases, and for
the uroflowmetry group is 23 cases. Considering a 10% loss to follow-up and refusal
rate, a minimum of 26 cases per group is required.
Statistical Analysis
Data analysis was conducted using SPSS 26.0 and R 4.4.0. Non-normally distributed
continuous variables were expressed as median with interquartile range (IQR), and
comparisons between groups were made using the Mann–Whitney test. Categorical variables
were expressed as frequencies and percentages, and comparisons between groups were
made using chi-square tests, Kappa tests, or Fisher's exact tests. Missing values
were replaced with the median. The receiver operating characteristic (ROC) curve was
used to evaluate the diagnostic efficacy of uroflowmetry for urethral stricture, with
the Youden index used to set the optimal cutoff value. Curve regression was used to
investigate the correlation between uroflowmetry and urethral calibration. A p -value of less than 0.05 was considered statistically significant.
Results
Baseline Characteristics
A total of 62 children were included in the study ([Fig. 1 ]), with 38 in the TIP group and 24 in the non-TIP group, followed up for a median
of 4.00 years (IQR 3.00–6.75). The median Qmax was 5.50 (IQR 3.50–7.50) ml/s in the TIP groups and 8.70 (IQR 6.60–10.62) ml/s in
the non-TIP groups, showing a statistically significant difference between the two
groups (p = 0.003). The median urethral calibration was 10.00 (IQR 9.25–11.00) Fr in the TIP
group and 11.00 (IQR 10.00–13.00) Fr in the non-TIP group, also showing a statistically
significant difference (p = 0.021). Ten children were diagnosed with urethral strictures. Baseline characteristics
are presented in [Table 1 ].
Table 1
Baseline characteristics
Variables
Total (n = 62)
TIP (n = 38)
Non-TIP (n = 24)
Statistic
p -value
Surgical information
Age at surgery (months), M (Q1 , Q3 )
15.00 (9.00, 31.50)
14.50 (8.25, 36.25)
15.00 (10.00, 23.00)
Z = − 0.06
0.949
Glans diameter (mm), M (Q1 , Q3 )
14.00 (13.00, 15.00)
14.00 (13.00, 16.50)
13.25 (13.00, 14.00)
Z = − 1.33
0.182
Degloved curvature, M (Q1 , Q3 )
20.00 (5.00, 45.00)
15.00 (2.50, 20.00)
60.00 (45.00, 90.00)
Z = − 4.97
<0.001
Urethral plate width (mm), M (Q1 , Q3 )
4.00 (2.50, 5.00)
4.00 (2.75, 5.00)
2.50 (2.00, 4.50)
Z = − 0.95
0.345
Meatus location[a ], n (%)
−
0.006
Proximal
18 (32.73)
7 (18.92)
11 (61.11)
Midshaft
30 (54.55)
25 (67.57)
5 (27.78)
Distal
7 (12.73)
5 (13.51)
2 (11.11)
Surgical techniques, n (%)
−
−
TIP
38 (61.29)
−
−
Non-TIP
24 (38.71)
−
−
One-stage Duckett
11 (45.83)
−
−
Staged Duckett
6 (25.00)
−
−
Duckett and Duplay
5 (20.83)
−
−
Onlay
1 (4.17)
−
−
Mathieu
1 (4.17)
−
−
Reconstruction length (mm), M (Q1 , Q3 )
25.00 (18.00, 40.00)
20.00 (15.00, 25.00)
40.00 (36.50, 46.25)
Z = − 5.42
<0.001
Uroflowmetry
Age at uroflowmetry (years), M (Q1 , Q3 )
4.00 (3.00, 6.75)
4.50 (3.00, 6.75)
4.00 (3.00, 5.50)
Z = − 0.30
0.764
Qmax , M (Q1 , Q3 )
6.60 (4.78, 9.50)
5.50 (3.50, 7.50)
8.70 (6.60, 10.62)
Z = − 2.92
0.003
Qave , M (Q1 , Q3 )
4.50 (3.10, 5.80)
4.05 (2.50, 4.68)
5.55 (4.45, 6.45)
Z = − 3.22
0.001
Calibration
Calibration, M (Q1 , Q3 )
10.00 (10.00, 12.00)
10.00 (9.25, 11.75)
11.00 (10.00, 13.00)
Z = − 2.06
0.040
Age at calibration (years), M (Q1 , Q3 )
4.00 (2.00, 6.00)
5.00 (3.00, 6.75)
3.00 (2.00, 5.00)
Z = − 1.34
0.180
Postoperative complications
Urethral fistula, n (%)
χ2 = 0.08
0.773
No
35 (56.45)
22 (57.89)
13 (54.17)
Yes
27 (43.55)
16 (42.11)
11 (45.83)
Urethral diverticulum, n (%)
χ2 = 3.69
0.055
No
56 (90.32)
37 (97.37)
19 (79.17)
Yes
6 (9.68)
1 (2.63)
5 (20.83)
Residual curve, n (%)
−
1.000
No
60 (96.77)
37 (97.37)
23 (95.83)
Yes
2 (3.23)
1 (2.63)
1 (4.17)
Abbreviations: −, Fisher's exact; M, median; Q1 , first quartile; Q3 , third quartile; Qave , average urinary flow rate; Qmax , maximum urinary flow rate; TIP, tubularized incised plate; Z, Mann − Whitney test;
χ2 , chi-square test.
a Only 55 cases were reported in the meatus location.
Fig. 1 Flow chart. TIP, tubularized incised plate.
Diagnostic Accuracy of Qmax and Qave for Urethral Stricture
ROC analysis was used to assess the diagnostic accuracy of Qmax and Qave for urethral strictures ([Supplementary Fig. S1 ] [available in the online version only]). In the non-TIP group, the area under the
curve (AUC) for Qmax was 0.94 (cutoff = 6.65 ml/s, sensitivity = 100%, specificity = 81.0%), higher than
that of Qave with 0.91 (cutoff = 4.95 ml/s, sensitivity = 100%, specificity = 71.4%). In the TIP
group, the AUC for Qmax was 0.80 (cutoff = 5.75 ml/s, sensitivity = 100%, specificity = 58.1%), higher than
that of Qave with 0.70 (cutoff = 3.20 ml/s, sensitivity = 71.4%, specificity = 67.7%).
Diagnostic Accuracy of Uroflowmetry Nomogram Intervals for Urethral Stricture
Uroflowmetry Siroky nomogram intervals Qmax ≤ −3SD, Qmax < − 2SD, Qave ≤ −3SD, and Qave < − 2SD were used to perform Kappa consistency tests for the diagnosis of urethral
stricture. In the non-TIP group, the Qmax nomogram interval ≤ −3 SD showed good consistency for the diagnosis of urethral stricture
(kappa = 0.70), with the ROC curve showing an AUC of 0.95 (cutoff = 0.5, sensitivity = 100%,
specificity = 91.0%; [Supplementary Fig. S1 ] [available in the online version only]). In contrast, the intervals Qmax < − 2SD, Qave ≤ −3SD, and Qave < − 2SD showed poor consistency for the diagnosis of urethral stricture (kappa = 0.29,
0.00, and 0.50, respectively). In the TIP group, the intervals Qmax ≤ −3SD, Qmax < − 2SD, Qave ≤ −3SD, and Qave < − 2SD also showed poor consistency for the diagnosis of urethral
stricture (kappa = 0.37, 0.13, −0.18, and 0.08, respectively).
Relationship between Uroflowmetry and Urethral Calibration
Curve regression analysis was used to examine the relationship between uroflowmetry
and urethral calibration ([Supplementary S2 ] [available in the online version only]). In the non-TIP group, a strong quadratic
correlation was found between urethral calibration and Qmax (C
2 = 14.72 * Qmax , R
2 = 0.96, p < 0.001), which was superior to the correlation in the TIP group (C
2 = 14.76 * Qmax , R
2 = 0.88, p < 0.001). Similarly, in the non-TIP group, a strong quadratic correlation was found
between urethral calibration and Qave (C
2 = 23.92 * Qave , R
2 = 0.96, p < 0.001), which was superior to the correlation in the TIP group (C
2 = 23.21 * Qave , R
2 = 0.87, p < 0.001).
Discussion
This study evaluates the diagnostic accuracy of uroflowmetry in detecting urethral
strictures following hypospadias repair in children. By comparing uroflowmetry results
with urethral calibration, we found that uroflowmetry, particularly Qmax , can effectively indicate the presence of urethral strictures in non-TIP patients.
For non-TIP patients with a urine flow rate lower than 6.65 ml/s, the presence of
urethral stricture should be considered. The diagnostic accuracy of urethral stricture
is superior when the nomogram interval is less than −3SD compared with −2SD. The use
of the formula C
2 = 14.72 * Qmax allows for the noninvasive estimation of urethral calibration. The diagnostic significance
of uroflowmetry for urethral strictures in TIP patients is limited, yet it still holds
considerable value for screening purposes. In summary, uroflowmetry can serve as a
routine follow-up procedure after hypospadias surgery to aid in the detection of urethral
strictures.
In the diagnosis of urethral strictures, methods like retrograde urethrography, cystoscopy,
urethral calibration, and uroflowmetry are commonly used.[11 ] Visual methods such as retrograde urethrography and cystoscopy show stricture details
but have low patient compliance (54.4%).[14 ] Urethral calibration, using a sound to measure urethral circumference, is a simple
diagnostic method for urethral strictures that can be performed in an outpatient setting.
Wein et al[7 ] and Snodgrass and Bush[15 ] suggest that calibration <8 Fr with urination symptoms indicates stricture. However,
some researchers find it hard to differentiate calibration from dilation due to potential
stricture dilation during the procedure.[16 ] Therefore, the current study defines calibration as the maximum size of sound entering
without significant resistance, breakthrough sensation, or severe pain for outpatients.
Considering the convenience of clinical application, urethral calibration was chosen
as the main diagnostic method, with only a few patients undergoing retrograde urethrography
and cystoscopy (not included in the data).
Uroflowmetry is being investigated as an independent diagnostic tool for urethral
stricture. Erickson et al[17 ] demonstrated that reduced uroflowmetry accompanied by urinary symptoms has 99% sensitivity
and 98% specificity for diagnosing urethral strictures. Yanagi et al[18 ] showed the effectiveness of uroflowmetry in predicting the anatomical success of
urethroplasty, with positive predictive values of 86% for Qmax and 87% for ΔQ (Qmax − Qave ). Considering that ΔQ may reflect urinary flow obstruction,[19 ] the current study included ΔQ in analyses, finding it not more accurate than Qmax , as detailed in [Supplements S3 ] and [S4 ] (available in the online version only). Lambert et al[20 ] established a predictive model for adult urethral strictures, using the equation
[1.675Ln(Qmax ) − 4.360Sqrt(ΔQ) + 4.146] to score patients, distinguishing healthy individuals from
those with urethral strictures. These studies highlight uroflowmetry's value, but
most were on adults, and pediatric data are lacking. Unlike adults, where posterior
strictures are common, children mostly have anterior strictures posthypospadias surgery.[21 ] This study proposed a noninvasive formula using Qmax for pediatric strictures, which holds practical significance for clinical application.
The results of this study indicate that in the non-TIP group, both Qmax and Qave have high sensitivity and specificity in diagnosing urethral strictures, with Qmax showing superior performance. Boroda et al[22 ] proposed that the repaired hypospadias urethra, especially those with longer tube
lengths, may not behave like a standard rigid tube, which could affect Qmax more significantly than Qave . Furthermore, our study indicates that the urinary flow rate nomogram interval of
less than −2SD does not effectively reflect the presence of urethral stricture. This
is likely because the standards for obstructive urination established from adult studies
are not applicable to children. A threshold of ≤ −3SD can effectively reflect urethral
stricture in children who have undergone non-TIP surgical techniques. This is important
because children have smaller bladders and urethras, leading to lower flow rates compared
with adults. Additionally, structural abnormalities are inherent in hypospadias cases
in children. Therefore, using a threshold of ≤ −3SD offers greater diagnostic accuracy
and sensitivity for urethral stricture compared with the < − 2SD.
The correlation between uroflowmetry and urethral calibration in TIP patients is not
as good as in non-TIP patients, which may be related to the “gourd-shaped” configuration
of the urethra[23 ] or decreased urethral compliance[10 ] following TIP surgery. Due to possible structural and/or functional abnormalities
of the urethral corpus spongiosum in children with hypospadias, the spongiosum is
limited in expansion during urination, leading to low uroflow rates. Nonetheless,
such abnormalities do not impact the outcomes of urethral calibration assessments.
While uroflowmetry's diagnostic value is limited, its 100% sensitivity and noninvasive
nature offer significant screening value. long-term observational studies have demonstrated
a substantial increase in uroflowmetry values during puberty for TIP patients. Consequently,
the uroflowmetry and urethral calibration of TIP patients may become more aligned
after puberty, which requires further follow-up studies to validate.[11 ]
[24 ]
This study has several limitations. First, as a retrospective study, the long follow-up
period and the fact that some patients were followed up locally led to missing data.
The use of median values to replace missing data may introduce information bias. Second,
uroflowmetry results can be affected by the volume of urine voided, making it difficult
to standardize the voided volume, which may impact the results. However, this study
analyzed the uroflowmetry nomogram intervals to minimize the influence of voided volume
on uroflowmetry results. Third, urethral calibration is not a routine examination
for patients with normal urine flow and urine flow rate, leading to a lack of a large
amount of normal urethral data and causing selection bias. Lastly, this study is based
on a single center with a small sample size, and it did not grade the severity of
urethral strictures, which limits the generalizability of the findings. Therefore,
future multicenter, large-sample, prospective cohort studies are needed to further
validate our findings and refine the diagnostic thresholds of uroflowmetry for urethral
strictures of varying severities.
Conclusion
Uroflowmetry, particularly Qmax , shows promise as a noninvasive screening tool for detecting urethral strictures
after hypospadias repair, with high diagnostic accuracy in non-TIP cases but limited
utility in TIP cases. Further multicenter prospective studies are needed to validate
these findings, refine diagnostic thresholds, and integrate uroflowmetry into standardized
pediatric follow-up protocols.
