Advertisement

Sexual function and lower urinary tract symptoms after minimally invasive endorectal pull-through in adolescent males with Hirschsprung disease

Open AccessPublished:September 24, 2022DOI:https://doi.org/10.1016/j.jpedsurg.2022.09.017

      Highlights

      • Knowledge about sexual function and the presence of lower urinary tract symptoms in Hirschsprung patients is very limited.
      • Such knowledge is very scarce after specifically minimally invasive endorectal pull-through.
      • Few studies have explored Hirschsprung males’ ability to ejaculate, and none has reported adolescents’ ability to ejaculate.
      • Minimally invasive endorectal pull-through seems to preserve erection and ejaculation in adolescent males.
      • Lower urinary tract symptoms are rare after minimally invasive endorectal pull-through in adolescent males.

      Abstract

      Background

      Effects of colorectal resection on sexual function and the lower urinary tract are inadequately studied in patients with Hirschsprung disease (HD). This study aimed to increase existing knowledge on sexual function and lower urinary tract symptoms (LUTS) in HD male adolescents operated with minimally invasive endorectal pull-through (ERPT).

      Methods

      Non-syndromic male adolescents (12–18 years) operated with ERPT were invited to participate in this single-center cross-sectional study which included a semi-structured interview on sexual function and LUTS, a questionnaire recording LUTS, and a urodynamic study. Uroflowmetry curves were eligible for evaluation if the voided volume was >50% of expected bladder capacity. Ethical approval and informed consent were obtained.

      Results

      Of 37 eligible male adolescents, 35 (95%) with a median age of 14.9 (12.0 -18.3) years were included. 94% had rectosigmoid aganglionosis, and 97% underwent a minimally invasive ERPT. 34 (97%) visited the outpatient clinic. The ability to get erections and to ejaculate was assessed in 25/35 (71%) adolescents. 25/25 (100%) could get an erection, and of adolescents ≥15 years 14/15 (93%) could ejaculate. 32 (91%) returned the questionnaire and underwent urodynamic studies. 15/32 (47%) reported LUTS, but most had only sporadic LUTS. 31/32 (97%) were highly satisfied with their bladder function. Sporadic urinary incontinence was reported by 4/32 (13%), but none reported social problems due to this. Of the eligible 28/32 (88%) uroflowmetry curves, 15/28 (54%) were normal.

      Conclusions

      Minimally invasive ERPT seems to preserve sexual function and does not induce lower urinary tract symptoms in adolescent HD males.

      Level of evidence

      III.

      Keywords

      Abbreviations:

      CAKUT (congenital anomalies of the kidney and urinary tract), DAN-PSS (danish prostatic symptom score), ERPT (endorectal pull-through), HD (Hirschsprung disease), LUTS (lower urinary tract symptoms), MCUG (micturating cystourethrogram)

      1. Introduction

      Hirschsprung disease (HD) is a rare congenital disorder that is characterized by the absence of ganglion cells in the lower digestive tract predominantly affecting males [
      • Tam P.K.
      • Garcia-Barcelo M.
      Genetic basis of Hirschsprung's disease.
      ]. Surgical management of HD involves removal of aganglionic bowel and restoration of bowel continuity. Rectal dissection is an integral part of any pull-through operation and has an inherent potential for injury to the urethra, bladder, ureters, sympathetic and parasympathetic lumbar nerves, prostate and spermatic cords in males and uterus, fallopian tubes, and ovaries in females. Damage to these structures may impaire sexual function and induce lower urinary tract symptoms (LUTS) [
      • Huber S.A.
      • Northington G.M.
      • Karp D.R.
      Bowel and bladder dysfunction following surgery within the presacral space: an overview of neuroanatomy, function, and dysfunction.
      ,
      • Boemers T.M.
      • Bax N.M.
      • van Gool J.D.
      The effect of rectosigmoidectomy and Duhamel-type pull-through procedure on lower urinary tract function in children with Hirschsprung's disease.
      . There is very limited knowledge about sexual function and frequency of LUTS after surgical management of HD, and specifically after minimally invasive endorectal pull-through techniques (ERPT). A systematic review from 2016 on sexual function and/or LUTS in HD patients found that only 24 studies had been published during the last 40 years [
      • Versteegh H.P.
      • Johal N.S.
      • de Blaauw I.
      • Stanton M.P.
      Urological and sexual outcome in patients with Hirschsprung disease: a systematic review.
      ]. The majority of these studies reported results after open surgery and multi-staged procedures. Ten studies, including 624 males, had assessed erectile and/or ejaculatory function, and sexual impairment was very rarely reported [
      • Weitzman J.J.
      • Hanson B.A.
      • Brennan L.P.
      Management of Hirschsprung's disease with the Swenson procedure.
      ,
      • Sherman J.O.
      • Snyder M.E.
      • Weitzman J.J.
      • Jona J.Z.
      • Gillis D.A.
      • O'Donnell B.
      • et al.
      A 40-year multinational retrospective study of 880 Swenson procedures.
      ,
      • Liem N.T.
      • Hau B.D.
      • Thu N.X.
      The long-term follow-up result of Swenson's operation in the treatment of Hirschsprung's disease in Vietnamese children.
      ,
      • Hau B.D.
      • Quynh T.A.
      • Anh V.H.
      • Liem N.T.
      Early and late outcomes of primary laparoscopic endorectal colon pull-through leaving a short rectal seromuscular sleeve for Hirschsprung disease.
      ]. In two more recent studies, sexual function was not different in 112 HD males and controls, while dyspareunia and subfertility were more frequent among 41 HD females compared to the controls [
      • Neuvonen M.
      • Kyrklund K.
      • Taskinen S.
      • Koivusalo A.
      • Rintala R.J.
      • Pakarinen M.P.
      Lower urinary tract symptoms and sexual functions after endorectal pull-through for Hirschsprung disease: controlled long-term outcomes.
      ,
      • Davidson J.R.
      • Kyrklund K.
      • Eaton S.
      • Pakarinen M.P.
      • Thompson D.S.
      • Cross K.
      • et al.
      Sexual function, quality of life, and fertility in women who had surgery for neonatal Hirschsprung's disease.
      . In the above mentioned review, 17 studies including 2546 patients of both genders found that less than 4% reported any type of LUTS [
      • Rassouli R.
      • Holschneider A.M.
      • Bolkenius M.
      • Menardi G.
      • Becker M.R.
      • Schaarschmidt K.
      • et al.
      Long-term results of Rehbein's procedure: a retrospective study in German-speaking countries.
      ,
      • Zhang S.C.
      • Bai Y.Z.
      • Wang W.
      • Wang W,L.
      Long-term outcome, colonic motility, and sphincter performance after Swenson's procedure for Hirschsprung's disease: a single-center 2-decade experience with 346 cases.
      ,
      • Pini Prato A.
      • Gentilino V.
      • Giunta C.
      • Avanzini S.
      • Parodi S.
      • Mattioli G.
      • et al.
      Hirschsprung's disease: 13 years' experience in 112 patients from a single institution.
      ,
      • Gunnarsdottir A.
      • Sandblom G.
      • Arnbjornsson E.
      • Larsson L.T.
      Quality of life in adults operated on for Hirschsprung disease in childhood.
      ]. Four more recent studies present contradictory results regarding LUTS; some found no difference between HD patients and controls, whereas others reported that HD patients with impaired bowel function had more frequent LUTS than other HD patients [
      • Neuvonen M.
      • Kyrklund K.
      • Taskinen S.
      • Koivusalo A.
      • Rintala R.J.
      • Pakarinen M.P.
      Lower urinary tract symptoms and sexual functions after endorectal pull-through for Hirschsprung disease: controlled long-term outcomes.
      ,
      • Granéli C.
      • Marschall Sima H.
      • Börjesson A.
      • Hagelsteen K.
      • Arnbjörnsson E.
      • Stenström P.
      Urinary tract anomalies and urinary tract dysfunction in children with Hirschsprung disease-Is follow-up indicated?.
      ,
      • Byström C.
      • Östlund S.
      • Hoff N.
      • Wester T.
      • Granström AL.
      Evaluation of bowel function, urinary tract function, and quality of life after transanal endorectal pull-through surgery for hirschsprung's disease.
      ,
      • Davidson J.R.
      • Kyrklund K.
      • Eaton S.
      • Pakarinen M.P.
      • Thompson D.S.
      • Cross K.
      • et al.
      Long-term surgical and patient-reported outcomes of Hirschsprung disease.
      ].
      In addition to the paucity of studies examining sexual function and LUTS in HD patients, few studies have applied validated questionnaires or had an independent investigator interviewing patients and doing the chart reviews. Most studies are retrospective and based on chart reviews only. Furthermore, the age distribution of the patients often varies greatly, making it difficult to draw conclusions [
      • Versteegh H.P.
      • Johal N.S.
      • de Blaauw I.
      • Stanton M.P.
      Urological and sexual outcome in patients with Hirschsprung disease: a systematic review.
      ,
      • Levitt M.A.
      • Hamrick M.C.
      • Eradi B.
      • Bischoff A.
      • Hall J.
      • Transanal PA.
      Full-thickness, Swenson-like approach for Hirschsprung disease.
      ,
      • Heikkinen M.
      • Rintala R.
      • Luukkonen P.
      Long-term anal sphincter performance after surgery for Hirschsprung's disease.
      ,
      • Puri P.
      • Nixon H.H.
      Long-term results of Swenson's operation for Hirschsprung's disease.
      ]. Therefore, the aim of this study was to increase existing knowledge on sexual function and frequency of LUTS in HD male adolescents operated with minimally invasive ERPT by having an independent investigator interviewing the patients, applying a validated questionnaire and performing urodynamic studies.

      2. Methods

      2.1 Study design

      This is a single-center cross-sectional study exploring sexual function and LUTS in male HD adolescents. Guidelines for Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) were applied [
      • von Elm E.
      • Altman D.G.
      • Egger M.
      • Pocock S.J.
      • Gøtzsche P.C.
      • Vandenbroucke J.P.
      The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies.
      ].

      2.2 Surgical techniques, perioperative examinations and follow-up routines

      Total transanal ERPT was performed mostly as described by de la Torre et al., but with a shorter mucosectomy [
      • De la Torre-Mondragón L.
      • Ortega-Salgado JA.
      Transanal endorectal pull-through for Hirschsprung's disease.
      ,
      • Rintala R.J.
      Transanal coloanal pull-through with a short muscular cuff for classic Hirschsprung's disease.
      . During laparoscopic assisted ERPT, the sigmoid colon and rectum were dissected down to the pelvic floor, and the mucosectomy was then performed transanally as in the total transanal technique.
      There was no systematic screening for urinary tract malformations. Investigations of the urinary tract had been done either because of urinary symptoms or because of prenatal findings. In addition, some had undergone abdominal ultrasound including examination of the urinary tract before HD was diagnosed as a part of investigations for gastrointestinal symptoms.
      Postoperative follow-up routines included frequent outpatient visits during the first year. Thereafter, frequency of outpatient visits depended on symptoms and availability for follow-up at the patients’ local hospital.

      2.3 Ethics

      Written informed consent was obtained from all adolescents ≥16 years and from parents of adolescents <16 years. Adolescents <16 years got age-adapted information about the study. The study was approved by the regional committee for medical and health research ethics (2018/2009) and the Hospital's Data Protection Officer (18/19101). The study is registered in Clinical Trials (NCT04106947).

      2.4 Patients, clinical setting and data collection

      All non-intellectually impaired male adolescents (12-18 years), fluent in Norwegian, having undergone ERPT and/or follow-up at our department were eligible for inclusion. Patients were identified from the hospital's electronic database and invited to participate by mail or during outpatient clinics.
      Demographics, length of the aganglionic segment, investigations of the urinary tract, presence of hypospadias, and surgical details were recorded retrospectively from electronic medical records. Congenital anomalies of the kidney and urinary tract (CAKUT) was defined as renal agenesis, kidney hypoplasia, hydronephrosis, and/or vesicoureteral reflux [
      • Pini Prato A.
      • Arnoldi R.
      • Falconi I.
      • Dusio M.P.
      • Ceccherini I.
      • Tentori A.
      • et al.
      Congenital anomalies of the kidney and urinary tract in a cohort of 280 consecutive patients with Hirschsprung disease.
      ].
      To register current clinical status, the adolescents had a semi-structured interview at the outpatient clinic, a clinical investigation if indicated, and urodynamic studies. They were also asked to answer a questionnaire recording LUTS. This questionnaire was a 12-item modified version of the Danish Prostatic Symptom Score (DAN-PSS) (Appendix 1) [
      • Hansen B.J.
      • Flyger H.
      • Brasso K.
      • Schou J.
      • Nordling J.
      • Thorup Andersen J.
      • et al.
      Validation of the self-administered danish prostatic symptom score (DAN-PSS-1) system for use in benign prostatic hyperplasia.
      ]. LUTS was defined as one or more of the following symptoms: voiding frequency >8/day, straining, urgency, urge incontinence, stress incontinence, incontinence without physical activity/straining (passive incontinence), and bedwetting (enuresis). Those who did not want to attend the outpatient clinic, could participate in the study by only answering the questionnaire which was sent by post.
      The semi-structured interviews were led by a surgeon who had not performed the ERPT operations or been responsible for the follow-up. The first part of the interview focused on current clinical status, including voiding habits and LUTS. All the adolescents were asked if they wanted to talk to the interviewer alone. If the adolescent and his parent(s) agreed, the interviewer talked with the adolescent alone from the age of 12. This was carried out as an informal conversation about sexual function. Sexual function was assessed by the adolescents’ self-reported ability to get erections and to ejaculate. Erection and ejaculation were reported dichotomously by the presence or absence of these functions.

      2.5 Urodynamic studies

      Uroflowmetry measuring flow rates and voiding volume was performed with the Flowstar Laborie/Medical Measurement Systems BV (MMS). Residual volume was measured by a suprapubic transcutaneous bladder scanning with the CUBEscan BioCon-700 by Mcube Technology. The uroflowmetry curves were considered reliable if the voided volume was >50% of expected bladder capacity [
      • Bauer S.B.
      • Nijman R.J.
      • Drzewiecki B.A.
      • Sillen U.
      • Hoebeke P.
      International Children's continence society standardization report on urodynamic studies of the lower urinary tract in children.
      ]. The flowmetry curves were examined by two independent investigators (ATH, RAK), and if they disagreed, a third investigator (KB) was consulted. The flowmetry curves were classified as normal (bell-shaped) or abnormal (non-bell-shaped: plateau-, staccato- or interrupted shaped) [
      • Bauer S.B.
      • Nijman R.J.
      • Drzewiecki B.A.
      • Sillen U.
      • Hoebeke P.
      International Children's continence society standardization report on urodynamic studies of the lower urinary tract in children.
      ].

      2.6 Statistics

      Continuous variables are presented as median (min-max). IBM SPSS software for Windows version 25 (Armonk, NY: IBM Corp.) was used.

      3. Results

      3.1 Adolescents

      Of 41 identified adolescents who had undergone ERPT, four had intellectual impairment. Consequently, 37 adolescents were invited to participate. Two did not respond, and 35 (95%) adolescents with a median age of 14.9 (12.0 -18.3) years were included. Thirty-four (97%) visited the outpatient clinic. Two (6%) had aganglionosis proximal to the rectosigmoid colon, and 34 (97%) were operated with minimally invasive techniques, either total transanal or laparoscopic assisted ERPT (Table 1). One adolescent had been operated abroad with laparotomy assisted ERPT, but follow up was done at our center. None of the patients had intraoperative urologic injury, postoperative anastomotic leakage or redo surgery.
      Table 1Demographics of male adolescents with Hirschsprung disease (n=35). One adolescent had more than one associated anomaly.
      Patients
      Age, median (min-max), years

      Length of aganglionosis

      Rectosigmoid colon

      Proximal to rectosigmoid colon

      Endorectal pull-through operations

      Total transanal

      Laparoscopy assisted

      Laparotomy assisted

      Associated anomalies

      Neurologic
      Hydrocephalus and a neurological disease without intellectual impairment.


      Urinary tract
      Kidney hypoplasia, hydronephrosis, and vesicoureteral reflux.


      Neoplasm
      Benign coecal tumor removed prior to diagnosis of Hirschsprung disease.
      14.9 (12-18.4)

      33 (94%)

      2 (6%)

      25 (71%)

      9 (26%)

      1 (3%)

      6 (15%)

      2 (5%)

      4 (10%)

      1 (3%)
      1 Hydrocephalus and a neurological disease without intellectual impairment.
      2 Kidney hypoplasia, hydronephrosis, and vesicoureteral reflux.
      3 Benign coecal tumor removed prior to diagnosis of Hirschsprung disease.

      3.2 Sexual function

      Twenty-seven adolescents agreed to talk to the interviewer about sexual function, but two adolescents (12 years) did not understand the questions and were excluded. Thus, 25/35 (71%) adolescents, median 15.4 (12.4-18.3) years, could be assessed for sexual function. All of the 25 adolescents reported that they could get erections.
      Eighteen of 25 (72%) adolescents, median 17.0 (13.3-18.3) years, told the interviewer that they could ejaculate. Of the adolescents ≥ 15 years, 14/15 (93%) could ejaculate. Seven adolescents, median 13.3 (12.4-15.9) years, knew they had not ejaculated. None of the adolescents reported retrograde ejaculation.

      3.3 Urology

      3.3.1 Investigations and operations in the urinary tract

      Seventeen of 35 (49%) adolescents had undergone one or more previous investigation of the urinary tract. Fifteen (88%) had undergone ultrasound, four (24%) uroflowmetry and measurement of residual volume, three (18%) a micturating cystourethrogram (MCUG), two (12%) scintigraphy, and one (6%) a cystometry.
      Ultrasound examinations had been normal in all but three. Findings in these three included unilateral hydronephrosis and hydroureter, unilateral hydroureter and a hypoplasic ipsilateral kidney, and isolated unilateral hydronephrosis. These three boys underwent further investigations. MCUG showed vesicoureteral reflux grade 3 and 4 in the two boys with hydroureter. Scintigraphy was performed in the same two boys and showed in both significantly reduced function in the ipsilateral kidney. The boy with isolated hydronephrosis got a repeat ultrasound showing no hydronephrosis. Two boys with initial normal ultrasonographic findings later underwent MCUG due to epididymo-orchitis and daytime urinary incontinence, and they had vesicoureteral reflux grade 0 and 2, respectively. Thus, four boys had six CAKUT: Kidney hypoplasia (1), hydronephrosis (2), and vesicoureteral reflux (3). None of the adolescent males had previously been diagnosed with hypospadia.
      Uroflowmetry and measurement of residual volume had been done previously in four boys because of neurologic disease without intellectual impairment, macroscopic hematuria and urinary tract infection, late onset bedwetting, and urinary hesitancy. Only the boy with a neurologic disease without intellectual impairment had a pathological uroflowmetry with large voided volumes, but no residual volumes. Cystometry in the same boy showed signs of a neurogenic bladder. Two boys underwent a urologic operation. Both had endoscopic Deflux®-injections due to vesicoureteral reflux.

      3.3.2 Lower urinary tract symptoms (LUTS)

      32/35 (91%) LUTS questionnaires were returned. 15/32 (47%) adolescents reported to have one or more LUTS, but the majority had only sporadic LUTS (Table 2). Urge, straining and any urinary incontinence occurred in 9/32 (28%), 8/32 (25%), and 4/32 (13%), respectively. None had bedwetting or social problems due to urinary incontinence. 31/32 (97%) adolescents reported high or excellent satisfaction with their bladder function. Low satisfaction with bladder function was noted in only one adolescent, and he had a neurologic disease without intellectual impairment.
      Table 2Results of selected items from a questionnaire on lower urinary tract symptoms answered by male adolescents operated for Hirschsprung disease (n=32).
      Daily micturitions1-3/day4-8/day>8/day
      11 (34%)20 (63%)1 (3%)
      Micturitions at nightNever1/night2/night≥3/night
      29 (91%)3 (9%)00
      NeverSeldomOftenAlways
      Straining24 (75%)7 (22%)1 (3%)0
      Urge23 (72%)7 (22%)2 (6%)0
      Urge incontinence31 (97%)1 (3%)00
      Stress incontinence29 (91%)3 (9%)00
      Passive incontinence31 (97%)1 (3%)00

      3.3.3 Findings from urodynamic studies

      Urodynamic studies were completed by 32/35 (91%) adolescents, but due to a technical problem only 31 curves could be evaluated. 28/31 (90%) had a voiding volume >50% of expected bladder capacity, and only the curves of these were examined (Table 3). The uroflowmetry curves were normal in 15/28 (54%). 7/28 (25%) had a plateau curve, 5/28 (18%) had a staccato curve, and 1/28 (4%) had an interrupted curve. 19/28 (68%) adolescents had a voided volume exceeding their expected bladder capacity. Of those with a plateau curve, all had a voided volume exceeding their expected bladder capacity.
      Table 3Results from urodynamic studies in male adolescents operated for Hirschsprung disease. Results are reported only for adolescents with a voided volume >50% of expected bladder capacity (n=28) and measured residual volume (n=26).
      Median (min-max)
      Voiding time (s)40 (15-72)
      Duration of flow (s)36 (15-70)
      Time to max flow (s)12 (2-32)
      Max flow rate (ml/s)26 (15-42)
      Mean flow rate (ml/s)16 (7-27)
      Voided volume (ml)517 (253-1060)
      Residual volume (ml)21 (0-193)

      3.4 Results from semi-structured interviews

      The interviews with the adolescents and parents together lasted from 60 to 90 min, whereas the interviews with the adolescents alone lasted from 5 to 30 min. Generally, the length of the interview with the adolescents increased by increasing age of the adolescent (results not shown).
      One of the first adolescents we interviewed, suggested that information regarding sexual function was not be reported in medical records available for the parents as this would make it easier to talk more freely. Subsequent adolescents were informed that data on sexual function would not be recorded in their medical records. None of the adolescents seemed to find it difficult or embarrassing to talk about sex, and they did not attempt to finish the conversation before it came to a natural ending. Several adolescents expressed concerns about the size and appearance of their penis. Furthermore, 3 (9%) adolescents attending the outpatient clinic had problems with phimosis. One was referred for surgical treatment, and two got conservative treatment.
      During the semi-structured interview voiding habits were investigated further as a supplement to the questionnaire on LUTS. Frequency of micturition was assessed by going through a normal day. We found that the rates of daily micturitions reported during semi-structured interviews and in the questionnaires were exactly the same. Overall, two thirds of the adolescents reported normal voiding habits. The twelve adolescents who reported <4 or >8 daily micturitions got advice how to normalize their voiding frequency. Those who had large residual volumes were advised to “double-void” morning and evening.

      4. Discussion

      The main finding of this study is that sexual function in adolescent HD males generally is unaffected by minimally invasive ERPT. Furthermore, sporadic LUTS were common, but patient satisfaction with bladder function was very high. This is important information to be passed on to patients and parents.
      The finding from this study on HD adolescent males’ ability to get an erection and to ejaculate contribute to the existing, but very limited knowledge on postoperative sexual function in HD males. The ability to get spontaneous erections after both open and minimally invasive ERPT, is reported in nearly 100% of HD males [
      • Weitzman J.J.
      • Hanson B.A.
      • Brennan L.P.
      Management of Hirschsprung's disease with the Swenson procedure.
      ,
      • Sherman J.O.
      • Snyder M.E.
      • Weitzman J.J.
      • Jona J.Z.
      • Gillis D.A.
      • O'Donnell B.
      • et al.
      A 40-year multinational retrospective study of 880 Swenson procedures.
      ,
      • Liem N.T.
      • Hau B.D.
      • Thu N.X.
      The long-term follow-up result of Swenson's operation in the treatment of Hirschsprung's disease in Vietnamese children.
      ,
      • Hau B.D.
      • Quynh T.A.
      • Anh V.H.
      • Liem N.T.
      Early and late outcomes of primary laparoscopic endorectal colon pull-through leaving a short rectal seromuscular sleeve for Hirschsprung disease.
      ,
      • Neuvonen M.
      • Kyrklund K.
      • Taskinen S.
      • Koivusalo A.
      • Rintala R.J.
      • Pakarinen M.P.
      Lower urinary tract symptoms and sexual functions after endorectal pull-through for Hirschsprung disease: controlled long-term outcomes.
      ,
      • Levitt M.A.
      • Hamrick M.C.
      • Eradi B.
      • Bischoff A.
      • Hall J.
      • Transanal PA.
      Full-thickness, Swenson-like approach for Hirschsprung disease.
      ,
      • Nielsen O.H.
      • Madsen C.M.
      13–25 Years follow-up after Swenson's operation for Hirschsprung's disease.
      ,
      • Ammar S.A.
      • Ibrahim I.A.
      One-stage transanal endorectal pull-through for treatment of hirschsprung's disease in adolescents and adults.
      . Thus, our results are in line with earlier studies. In contrast to the number of studies examining the ability to get spontaneous erections, very few studies have explored HD males’ ability to ejaculate, and none has reported adolescents’ ability to ejaculate. We found that nearly all adolescents ≥15 years could ejaculate and none reported to have a retrograde ejaculation. A recent study in 16 adult HD males who had undergone ERPT in childhood, found that all could ejaculate and the first ejaculation occurred at median 13 years [
      • Neuvonen M.
      • Kyrklund K.
      • Taskinen S.
      • Koivusalo A.
      • Rintala R.J.
      • Pakarinen M.P.
      Lower urinary tract symptoms and sexual functions after endorectal pull-through for Hirschsprung disease: controlled long-term outcomes.
      ]. Studies from the 1970s including patients operated with the open Swenson procedure report absent ejaculation in a few patients [
      • Puri P.
      • Nixon H.H.
      Long-term results of Swenson's operation for Hirschsprung's disease.
      ,
      • Nielsen O.H.
      • Madsen C.M.
      13–25 Years follow-up after Swenson's operation for Hirschsprung's disease.
      . A recent study found that 2% of 94 adult HD males had retrograde ejaculation after mostly open Duhamel pull-through [
      • Davidson J.R.
      • Kyrklund K.
      • Eaton S.
      • Pakarinen M.P.
      • Thompson D.S.
      • Cross K.
      • et al.
      Sexual function, quality of life, and fertility in women who had surgery for neonatal Hirschsprung's disease.
      ]. Since so few studies have explored ejaculation in HD males, one cannot draw any firm conclusions, but it seems that the ability to ejaculate is preserved in the great majority of HD males.
      In a previous qualitative study we reported that adult HD males expressed good sexual self-esteem and few problems with intimate relationships [
      • Hoel A.T.
      • Tofft L.
      • Bjørnland K.
      • Gjone H.
      • Teig C.J.
      • Øresland T.
      • et al.
      Reaching adulthood with Hirschsprung's disease: patient experiences and recommendations for transitional care.
      ]. This is supported by a recent quantitative study reporting that sexual quality of life in adult HD males was comparable to controls [
      • Davidson J.R.
      • Kyrklund K.
      • Eaton S.
      • Pakarinen M.P.
      • Thompson D.S.
      • Cross K.
      • et al.
      Sexual function, quality of life, and fertility in women who had surgery for neonatal Hirschsprung's disease.
      ]. The HD men in our previous study recommended addressing sex from early teens during follow-up and explain to the teenagers how the operation could interfere with later sexual activity. Some had wondered if they should take any precautions concerning sexual activities because of previous surgery. Based on this and the experience from talking about sex with the HD adolescents, we suggest that sex is discussed with HD teens.
      LUTS were reported by nearly half of the male HD adolescents, but the majority had only sporadic LUTS. This observation is in accordance with recent studies which report LUTS in 37-68% of HD patients of both genders operated with ERPT [
      • Neuvonen M.
      • Kyrklund K.
      • Taskinen S.
      • Koivusalo A.
      • Rintala R.J.
      • Pakarinen M.P.
      Lower urinary tract symptoms and sexual functions after endorectal pull-through for Hirschsprung disease: controlled long-term outcomes.
      ,
      • Granéli C.
      • Marschall Sima H.
      • Börjesson A.
      • Hagelsteen K.
      • Arnbjörnsson E.
      • Stenström P.
      Urinary tract anomalies and urinary tract dysfunction in children with Hirschsprung disease-Is follow-up indicated?.
      ,
      • Byström C.
      • Östlund S.
      • Hoff N.
      • Wester T.
      • Granström AL.
      Evaluation of bowel function, urinary tract function, and quality of life after transanal endorectal pull-through surgery for hirschsprung's disease.
      . As shown in a large population study, we report urge and stress incontinence in very few adolescent HD males [
      • Kyrklund K.
      • Taskinen S.
      • Rintala R.J.
      • Pakarinen M.P.
      Lower urinary tract symptoms from childhood to adulthood: a population based study of 594 Finnish individuals 4 to 26 years old.
      ]. Overall, we found that one out of ten male HD adolescents had urinary incontinence. This is in line with a systematic review where urinary incontinence was found in up to 11% of patients after open and minimally invasive ERPT [
      • Versteegh H.P.
      • Johal N.S.
      • de Blaauw I.
      • Stanton M.P.
      Urological and sexual outcome in patients with Hirschsprung disease: a systematic review.
      ]. None of the adolescents reported social problems related to urinary incontinence which is in accordance with other studies [
      • Neuvonen M.
      • Kyrklund K.
      • Taskinen S.
      • Koivusalo A.
      • Rintala R.J.
      • Pakarinen M.P.
      Lower urinary tract symptoms and sexual functions after endorectal pull-through for Hirschsprung disease: controlled long-term outcomes.
      ,
      • Granéli C.
      • Marschall Sima H.
      • Börjesson A.
      • Hagelsteen K.
      • Arnbjörnsson E.
      • Stenström P.
      Urinary tract anomalies and urinary tract dysfunction in children with Hirschsprung disease-Is follow-up indicated?.
      ,
      • Byström C.
      • Östlund S.
      • Hoff N.
      • Wester T.
      • Granström AL.
      Evaluation of bowel function, urinary tract function, and quality of life after transanal endorectal pull-through surgery for hirschsprung's disease.
      . We found that none of the adolescents had enuresis. Another study reported increased frequency of enuresis in HD patients compared to the age-matched controls, but the HD patients in that study were young; median 8 years [
      • Granéli C.
      • Marschall Sima H.
      • Börjesson A.
      • Hagelsteen K.
      • Arnbjörnsson E.
      • Stenström P.
      Urinary tract anomalies and urinary tract dysfunction in children with Hirschsprung disease-Is follow-up indicated?.
      ]. Recent large studies have found that enuresis are more common in constipated HD children, and that poor bowel function is associated with frequent urinary incontinence regardless of age [
      • Granéli C.
      • Marschall Sima H.
      • Börjesson A.
      • Hagelsteen K.
      • Arnbjörnsson E.
      • Stenström P.
      Urinary tract anomalies and urinary tract dysfunction in children with Hirschsprung disease-Is follow-up indicated?.
      ,
      • Davidson J.R.
      • Mutanen A.
      • Salli M.
      • Kyrklund K.
      • De Coppi P.
      • Curry J.
      • et al.
      Comparative cohort study of Duhamel and endorectal pull-through for Hirschsprung's disease.
      . It is well known that both hypospadia and neurologic diseases, especially in the central nervous system, could affect patients’ LUTS-profile negatively [
      • Rynja S.P.
      • de Jong T.P.
      • Bosch J.L.
      • de Kort L.M.
      Functional, cosmetic and psychosexual results in adult men who underwent hypospadias correction in childhood.
      ,
      • Averbeck M.A.
      • Madersbacher H.
      Follow-up of the neuro-urological patient: a systematic review.
      . One male adolescent had a neurologic disease without intellectual impairment, and was the only one with low satisfaction with own bladder function. It is also important to emphasize that the frequency of LUTS in this and most studies we have compared our results with, report findings in non-syndromic HD patients [
      • Neuvonen M.
      • Kyrklund K.
      • Taskinen S.
      • Koivusalo A.
      • Rintala R.J.
      • Pakarinen M.P.
      Lower urinary tract symptoms and sexual functions after endorectal pull-through for Hirschsprung disease: controlled long-term outcomes.
      ,
      • Granéli C.
      • Marschall Sima H.
      • Börjesson A.
      • Hagelsteen K.
      • Arnbjörnsson E.
      • Stenström P.
      Urinary tract anomalies and urinary tract dysfunction in children with Hirschsprung disease-Is follow-up indicated?.
      ,
      • Bjornland K.
      • Pakarinen M.P.
      • Stenstrom P.
      • Stensrud K.J.
      • Neuvonen M.
      • Granstrom A.L.
      • et al.
      A Nordic multicenter survey of long-term bowel function after transanal endorectal pull-through in 200 patients with rectosigmoid Hirschsprung disease.
      . In syndromic HD patients, both frequency and severity of LUTS are different from those without a syndrome [
      • Dingemans A.J.M.
      • Reck-Burneo C.A.
      • Fuchs M.
      • Sanchez A.V.
      • Lane V.A.
      • Hoover E.
      • et al.
      Urinary outcomes in patients with down's syndrome and Hirschsprung's disease.
      ,
      • Davidson J.R.
      • Kyrklund K.
      • Eaton S.
      • Pakarinen M.P.
      • Thompson D.
      • Blackburn S.C.
      • et al.
      Outcomes in Hirschsprung's disease with coexisting learning disability.
      .
      Very few papers report results from postoperative urodynamic studies in HD patients, and only one recent study presents findings from urodynamic studies after minimally invasive ERPT [
      • Neuvonen M.
      • Kyrklund K.
      • Taskinen S.
      • Koivusalo A.
      • Rintala R.J.
      • Pakarinen M.P.
      Lower urinary tract symptoms and sexual functions after endorectal pull-through for Hirschsprung disease: controlled long-term outcomes.
      ]. Interestingly, only half of the uroflowmetry curves were normal (bell-shaped) in both studies. In contrast, two large studies of 1268 and 950 healthy children aged 4-14 years report 80-90% normal curves [
      • Franco I.
      • Shei-Dei Yang S.
      • Chang S.J.
      • Nussenblatt B.
      • Franco J.A.
      A quantitative approach to the interpretation of uroflowmetry in children.
      ,
      • Gutierrez Segura C.
      Urine flow in childhood: a study of flow chart parameters based on 1,361 uroflowmetry tests.
      . The HD adolescents’ frequency of staccato and interrupted curves were not different from healthy controls, but plateau curves were more common. Plateau curves are found in 5% of healthy controls, and often when voided volumes are large [
      • Gierup J.
      Micturition studies in infants and children normal urinary flow.
      ]. The majority of the adolescents in our study had voided volumes exceeding their expected bladder capacity. The most plausible explanation is that they waited too long before they voided as most reported a strong urge to void. If we had done a second urodynamic study, this source of error might have been ruled out.
      There is a growing recognition that HD is associated with CAKUT. CAKUT occur in 4-25% of HD patients compared to 0.3-1.7% in the general population [
      • Pini Prato A.
      • Arnoldi R.
      • Falconi I.
      • Dusio M.P.
      • Ceccherini I.
      • Tentori A.
      • et al.
      Congenital anomalies of the kidney and urinary tract in a cohort of 280 consecutive patients with Hirschsprung disease.
      ,
      • Hofmann A.D.
      • Duess J.W.
      • Puri P.
      Congenital anomalies of the kidney and urinary tract (CAKUT) associated with Hirschsprung's disease: a systematic review.
      ,
      • Moore S.W.
      The contribution of associated congenital anomalies in understanding Hirschsprung's disease.
      ,
      • Prato A.P.
      • Musso M.
      • Ceccherini I.
      • Mattioli G.
      • Giunta C.
      • Ghiggeri G.M.
      • et al.
      Hirschsprung disease and congenital anomalies of the kidney and urinary tract (CAKUT): a novel syndromic association.
      ,
      • Amiel J.
      • Sproat-Emison E.
      • Garcia-Barcelo M.
      • Lantieri F.
      • Burzynski G.
      • Borrego S.
      • et al.
      Hirschsprung disease, associated syndromes and genetics: a review.
      ,
      • Tain Y.L.
      • Luh H.
      • Lin C.Y.
      • Hsu C.N.
      Incidence and risks of congenital anomalies of kidney and urinary tract in newborns: a population-based case-control study in Taiwan.
      ,
      • Melo B.F.
      • Aguiar M.B.
      • Bouzada M.C.
      • Aguiar R.L.
      • Pereira A.K.
      • Paixão G.M.
      • et al.
      Early risk factors for neonatal mortality in CAKUT: analysis of 524 affected newborns.
      ]. Among those who had investigations of the urinary tract, we found that 24% fulfilled the criteria for CAKUT. This percentage is probably not reflecting the true frequency of CAKUT in this population because there was no systematic screening and several investigations had been done due to urinary symptoms or prenatal findings. Many studies advocate that all HD patients should be screened for CAKUT. Whether this is beneficial is debatable, as few with CAKUT need any treatment [
      • Granéli C.
      • Marschall Sima H.
      • Börjesson A.
      • Hagelsteen K.
      • Arnbjörnsson E.
      • Stenström P.
      Urinary tract anomalies and urinary tract dysfunction in children with Hirschsprung disease-Is follow-up indicated?.
      ,
      • Hofmann A.D.
      • Duess J.W.
      • Puri P.
      Congenital anomalies of the kidney and urinary tract (CAKUT) associated with Hirschsprung's disease: a systematic review.
      ,
      • Prato A.P.
      • Musso M.
      • Ceccherini I.
      • Mattioli G.
      • Giunta C.
      • Ghiggeri G.M.
      • et al.
      Hirschsprung disease and congenital anomalies of the kidney and urinary tract (CAKUT): a novel syndromic association.
      . Only 6% of the adolescents in this study had undergone an operation due to CAKUT. This is in line with other studies which find that only a minority of HD patients with CAKUT required medical or surgical treatment [
      • Granéli C.
      • Marschall Sima H.
      • Börjesson A.
      • Hagelsteen K.
      • Arnbjörnsson E.
      • Stenström P.
      Urinary tract anomalies and urinary tract dysfunction in children with Hirschsprung disease-Is follow-up indicated?.
      ,
      • Pini Prato A.
      • Arnoldi R.
      • Falconi I.
      • Dusio M.P.
      • Ceccherini I.
      • Tentori A.
      • et al.
      Congenital anomalies of the kidney and urinary tract in a cohort of 280 consecutive patients with Hirschsprung disease.
      ,
      • Renda R.
      Renal outcome of congenital anomalies of the kidney and urinary tract system: a single-center retrospective study.
      ,
      • Çetinkaya P.G.
      • Gülhan B.
      • Düzova A.
      • Beşbaş N.
      • Hayran M.
      • Topaloğlu R.
      • et al.
      Clinical characteristics of children with congenital anomalies of the kidney and urinary tract and predictive factors of chronic kidney disease.
      .
      The main strengths of this study are the high rate of attendance and that an independent investigator interviewed the adolescents and their parents and did the chart reviews. The use of a validated questionnaire and urodynamic studies also strengthen the generalizability. The modified version of the DAN-PSS have been extensively used to report LUTS in HD patients and controls, thereby making it easier to compare and contextualize the results from this present study with other studies in HD patients [
      • Neuvonen M.
      • Kyrklund K.
      • Taskinen S.
      • Koivusalo A.
      • Rintala R.J.
      • Pakarinen M.P.
      Lower urinary tract symptoms and sexual functions after endorectal pull-through for Hirschsprung disease: controlled long-term outcomes.
      ,
      • Byström C.
      • Östlund S.
      • Hoff N.
      • Wester T.
      • Granström AL.
      Evaluation of bowel function, urinary tract function, and quality of life after transanal endorectal pull-through surgery for hirschsprung's disease.
      ,
      • Kyrklund K.
      • Taskinen S.
      • Rintala R.J.
      • Pakarinen M.P.
      Lower urinary tract symptoms from childhood to adulthood: a population based study of 594 Finnish individuals 4 to 26 years old.
      ,
      • Davidson J.R.
      • Mutanen A.
      • Salli M.
      • Kyrklund K.
      • De Coppi P.
      • Curry J.
      • et al.
      Comparative cohort study of Duhamel and endorectal pull-through for Hirschsprung's disease.
      ,
      • Davidson J.R.
      • Kyrklund K.
      • Eaton S.
      • Pakarinen M.P.
      • Thompson D.S.
      • Cross K.
      • et al.
      Long-term surgical and patient-reported outcomes of Hirschsprung's Disease.
      . We did not use a questionnaire to evaluate sexual function. It is possible that the adolescents would have answered more honest if a questionnaire had been used. In addition, some may regard asking 12-14 year old male adolescents about sexual function a limitation. Based on the adolescents’ reporting on sexual function, one could talk about sexual function from the age of 12, but study male patients’ sexual function at a higher age.
      To conclude, this study suggests that minimally invasive ERPT preserves sexual function and does not induce lower urinary tract symptoms in adolescent HD males. Furthermore, male HD adolescents appreciate the opportunity to talk about sex, and this should be a part of transitional care.

      Declaration of Competing Interest

      The authors report no conflict of interest.

      Acknowledgments

      We would like to thank stoma nurses Astrid Austrheim and Hanne Ambrose for their work in data collection and Tom Øresland for proof reading.

      Funding

      The study was funded by the Norwegian Dam Foundation.

      Appendix. Supplementary materials

      References

        • Tam P.K.
        • Garcia-Barcelo M.
        Genetic basis of Hirschsprung's disease.
        Pediatr Surg Int. 2009; 25: 543-558
        • Huber S.A.
        • Northington G.M.
        • Karp D.R.
        Bowel and bladder dysfunction following surgery within the presacral space: an overview of neuroanatomy, function, and dysfunction.
        Int Urogynecol J. 2015; 26: 941-946
        • Boemers T.M.
        • Bax N.M.
        • van Gool J.D.
        The effect of rectosigmoidectomy and Duhamel-type pull-through procedure on lower urinary tract function in children with Hirschsprung's disease.
        J Pediatr Surg. 2001; 36: 453-456
        • Versteegh H.P.
        • Johal N.S.
        • de Blaauw I.
        • Stanton M.P.
        Urological and sexual outcome in patients with Hirschsprung disease: a systematic review.
        J Pediatr Urol. 2016; 12: 352-360
        • Weitzman J.J.
        • Hanson B.A.
        • Brennan L.P.
        Management of Hirschsprung's disease with the Swenson procedure.
        J Pediatr Surg. 1972; 7: 157-162
        • Sherman J.O.
        • Snyder M.E.
        • Weitzman J.J.
        • Jona J.Z.
        • Gillis D.A.
        • O'Donnell B.
        • et al.
        A 40-year multinational retrospective study of 880 Swenson procedures.
        J Pediatr Surg. 1989; 24: 833-838
        • Liem N.T.
        • Hau B.D.
        • Thu N.X.
        The long-term follow-up result of Swenson's operation in the treatment of Hirschsprung's disease in Vietnamese children.
        Eur J Pediatric Surg. 1995; 5 (official journal of Austrian Association of Pediatric Surgery [et al] = Zeitschrift fur Kinderchirurgie): 110-112
        • Hau B.D.
        • Quynh T.A.
        • Anh V.H.
        • Liem N.T.
        Early and late outcomes of primary laparoscopic endorectal colon pull-through leaving a short rectal seromuscular sleeve for Hirschsprung disease.
        J Laparoendosc Adv Surg Techn Part A. 2011; 21: 81-83
        • Neuvonen M.
        • Kyrklund K.
        • Taskinen S.
        • Koivusalo A.
        • Rintala R.J.
        • Pakarinen M.P.
        Lower urinary tract symptoms and sexual functions after endorectal pull-through for Hirschsprung disease: controlled long-term outcomes.
        J Pediatr Surg. 2017; 52: 1296-1301
        • Davidson J.R.
        • Kyrklund K.
        • Eaton S.
        • Pakarinen M.P.
        • Thompson D.S.
        • Cross K.
        • et al.
        Sexual function, quality of life, and fertility in women who had surgery for neonatal Hirschsprung's disease.
        Br J Surg. 2021; 108: e79-e80
        • Rassouli R.
        • Holschneider A.M.
        • Bolkenius M.
        • Menardi G.
        • Becker M.R.
        • Schaarschmidt K.
        • et al.
        Long-term results of Rehbein's procedure: a retrospective study in German-speaking countries.
        Eur J Pediatric Surg. 2003; 13 (official journal of Austrian Association of Pediatric Surgery [et al] = Zeitschrift fur Kinderchirurgie): 187-194
        • Zhang S.C.
        • Bai Y.Z.
        • Wang W.
        • Wang W,L.
        Long-term outcome, colonic motility, and sphincter performance after Swenson's procedure for Hirschsprung's disease: a single-center 2-decade experience with 346 cases.
        Am J Surg. 2007; 194: 40-47
        • Pini Prato A.
        • Gentilino V.
        • Giunta C.
        • Avanzini S.
        • Parodi S.
        • Mattioli G.
        • et al.
        Hirschsprung's disease: 13 years' experience in 112 patients from a single institution.
        Pediatr Surg Int. 2008; 24: 175-182
        • Gunnarsdottir A.
        • Sandblom G.
        • Arnbjornsson E.
        • Larsson L.T.
        Quality of life in adults operated on for Hirschsprung disease in childhood.
        J Pediatr Gastroenterol Nutr. 2010; 51: 160-166
        • Granéli C.
        • Marschall Sima H.
        • Börjesson A.
        • Hagelsteen K.
        • Arnbjörnsson E.
        • Stenström P.
        Urinary tract anomalies and urinary tract dysfunction in children with Hirschsprung disease-Is follow-up indicated?.
        J Pediatr Surg. 2019; 54: 2012-2016
        • Byström C.
        • Östlund S.
        • Hoff N.
        • Wester T.
        • Granström AL.
        Evaluation of bowel function, urinary tract function, and quality of life after transanal endorectal pull-through surgery for hirschsprung's disease.
        Eur J Pediatric Surg. 2021; 31 (official journal of Austrian Association of Pediatric Surgery [et al] = Zeitschrift fur Kinderchirurgie): 40-48
        • Davidson J.R.
        • Kyrklund K.
        • Eaton S.
        • Pakarinen M.P.
        • Thompson D.S.
        • Cross K.
        • et al.
        Long-term surgical and patient-reported outcomes of Hirschsprung disease.
        J Pediatr Surg. 2021; 56: 1502-1511
        • Levitt M.A.
        • Hamrick M.C.
        • Eradi B.
        • Bischoff A.
        • Hall J.
        • Transanal PA.
        Full-thickness, Swenson-like approach for Hirschsprung disease.
        J Pediatr Surg. 2013; 48: 2289-2295
        • Heikkinen M.
        • Rintala R.
        • Luukkonen P.
        Long-term anal sphincter performance after surgery for Hirschsprung's disease.
        J Pediatr Surg. 1997; 32: 1443-1446
        • Puri P.
        • Nixon H.H.
        Long-term results of Swenson's operation for Hirschsprung's disease.
        Prog Pediatr Surg. 1977; 10: 87-96
        • von Elm E.
        • Altman D.G.
        • Egger M.
        • Pocock S.J.
        • Gøtzsche P.C.
        • Vandenbroucke J.P.
        The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies.
        Lancet. 2007; 370: 1453-1457
        • De la Torre-Mondragón L.
        • Ortega-Salgado JA.
        Transanal endorectal pull-through for Hirschsprung's disease.
        J Pediatr Surg. 1998; 33: 1283-1286
        • Rintala R.J.
        Transanal coloanal pull-through with a short muscular cuff for classic Hirschsprung's disease.
        Eur J Pediatric Surg. 2003; 13 (official journal of Austrian Association of Pediatric Surgery [et al] = Zeitschrift fur Kinderchirurgie): 181-186
        • Pini Prato A.
        • Arnoldi R.
        • Falconi I.
        • Dusio M.P.
        • Ceccherini I.
        • Tentori A.
        • et al.
        Congenital anomalies of the kidney and urinary tract in a cohort of 280 consecutive patients with Hirschsprung disease.
        Pediatr Nephrol. 2021; 36: 3151-3158
        • Hansen B.J.
        • Flyger H.
        • Brasso K.
        • Schou J.
        • Nordling J.
        • Thorup Andersen J.
        • et al.
        Validation of the self-administered danish prostatic symptom score (DAN-PSS-1) system for use in benign prostatic hyperplasia.
        Br J Urol. 1995; 76: 451-458
        • Bauer S.B.
        • Nijman R.J.
        • Drzewiecki B.A.
        • Sillen U.
        • Hoebeke P.
        International Children's continence society standardization report on urodynamic studies of the lower urinary tract in children.
        Neurourol Urodyn. 2015; 34: 640-647
        • Nielsen O.H.
        • Madsen C.M.
        13–25 Years follow-up after Swenson's operation for Hirschsprung's disease.
        Prog Pediatr Surg. 1977; 10: 97-102
        • Ammar S.A.
        • Ibrahim I.A.
        One-stage transanal endorectal pull-through for treatment of hirschsprung's disease in adolescents and adults.
        J Gastrointest Surg Off J Soc Surg Aliment Tract. 2011; 15: 2246-2250
        • Hoel A.T.
        • Tofft L.
        • Bjørnland K.
        • Gjone H.
        • Teig C.J.
        • Øresland T.
        • et al.
        Reaching adulthood with Hirschsprung's disease: patient experiences and recommendations for transitional care.
        J Pediatr Surg. 2021; 56: 257-262
        • Kyrklund K.
        • Taskinen S.
        • Rintala R.J.
        • Pakarinen M.P.
        Lower urinary tract symptoms from childhood to adulthood: a population based study of 594 Finnish individuals 4 to 26 years old.
        J Urol. 2012; 188: 588-593
        • Davidson J.R.
        • Mutanen A.
        • Salli M.
        • Kyrklund K.
        • De Coppi P.
        • Curry J.
        • et al.
        Comparative cohort study of Duhamel and endorectal pull-through for Hirschsprung's disease.
        BJS open. 2022; 6
        • Rynja S.P.
        • de Jong T.P.
        • Bosch J.L.
        • de Kort L.M.
        Functional, cosmetic and psychosexual results in adult men who underwent hypospadias correction in childhood.
        J Pediatr Urol. 2011; 7: 504-515
        • Averbeck M.A.
        • Madersbacher H.
        Follow-up of the neuro-urological patient: a systematic review.
        BJU Int. 2015; 115: 39-46
        • Bjornland K.
        • Pakarinen M.P.
        • Stenstrom P.
        • Stensrud K.J.
        • Neuvonen M.
        • Granstrom A.L.
        • et al.
        A Nordic multicenter survey of long-term bowel function after transanal endorectal pull-through in 200 patients with rectosigmoid Hirschsprung disease.
        J Pediatr Surg. 2017; 52: 1458-1464
        • Dingemans A.J.M.
        • Reck-Burneo C.A.
        • Fuchs M.
        • Sanchez A.V.
        • Lane V.A.
        • Hoover E.
        • et al.
        Urinary outcomes in patients with down's syndrome and Hirschsprung's disease.
        Eur J Pediatric Surg. 2019; 29 (official journal of Austrian Association of Pediatric Surgery [et al] = Zeitschrift fur Kinderchirurgie): 378-383
        • Davidson J.R.
        • Kyrklund K.
        • Eaton S.
        • Pakarinen M.P.
        • Thompson D.
        • Blackburn S.C.
        • et al.
        Outcomes in Hirschsprung's disease with coexisting learning disability.
        Eur J Pediatr. 2021; 180: 3499-3507
        • Franco I.
        • Shei-Dei Yang S.
        • Chang S.J.
        • Nussenblatt B.
        • Franco J.A.
        A quantitative approach to the interpretation of uroflowmetry in children.
        Neurourol Urodyn. 2016; 35: 836-846
        • Gutierrez Segura C.
        Urine flow in childhood: a study of flow chart parameters based on 1,361 uroflowmetry tests.
        J Urol. 1997; 157: 1426-1428
        • Gierup J.
        Micturition studies in infants and children normal urinary flow.
        Scand J Urol Nephrol. 1970; 4: 191-197
        • Hofmann A.D.
        • Duess J.W.
        • Puri P.
        Congenital anomalies of the kidney and urinary tract (CAKUT) associated with Hirschsprung's disease: a systematic review.
        Pediatr Surg Int. 2014; 30: 757-761
        • Moore S.W.
        The contribution of associated congenital anomalies in understanding Hirschsprung's disease.
        Pediatr Surg Int. 2006; 22: 305-315
        • Prato A.P.
        • Musso M.
        • Ceccherini I.
        • Mattioli G.
        • Giunta C.
        • Ghiggeri G.M.
        • et al.
        Hirschsprung disease and congenital anomalies of the kidney and urinary tract (CAKUT): a novel syndromic association.
        Medicine. 2009; 88 (Baltimore): 83-90
        • Amiel J.
        • Sproat-Emison E.
        • Garcia-Barcelo M.
        • Lantieri F.
        • Burzynski G.
        • Borrego S.
        • et al.
        Hirschsprung disease, associated syndromes and genetics: a review.
        J Med Genet. 2008; 45: 1-14
        • Tain Y.L.
        • Luh H.
        • Lin C.Y.
        • Hsu C.N.
        Incidence and risks of congenital anomalies of kidney and urinary tract in newborns: a population-based case-control study in Taiwan.
        Medicine. 2016; 95 (Baltimore): e2659
        • Melo B.F.
        • Aguiar M.B.
        • Bouzada M.C.
        • Aguiar R.L.
        • Pereira A.K.
        • Paixão G.M.
        • et al.
        Early risk factors for neonatal mortality in CAKUT: analysis of 524 affected newborns.
        Pediatr Nephrol. 2012; 27: 965-972
        • Renda R.
        Renal outcome of congenital anomalies of the kidney and urinary tract system: a single-center retrospective study.
        Minerva Urol Nefrol. 2018; 70: 218-225
        • Çetinkaya P.G.
        • Gülhan B.
        • Düzova A.
        • Beşbaş N.
        • Hayran M.
        • Topaloğlu R.
        • et al.
        Clinical characteristics of children with congenital anomalies of the kidney and urinary tract and predictive factors of chronic kidney disease.
        Turk J Pediatr. 2020; 62: 746-755
        • Davidson J.R.
        • Kyrklund K.
        • Eaton S.
        • Pakarinen M.P.
        • Thompson D.S.
        • Cross K.
        • et al.
        Long-term surgical and patient-reported outcomes of Hirschsprung's Disease.
        J Pediatr Surg. 2021;