Childhood outcome after correction of long-gap esophageal atresia by thoracoscopic external traction technique

  • E. Sofie van Tuyll van Serooskerken
    Affiliations
    Congenital Esophageal and Airway Team Utrecht, Department of Pediatric Surgery, Wilhelmina Children's Hospital, University Medical Center Utrecht, P.O. Box 85090, AB Utrecht 3508, the Netherlands
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  • Maud Y.A. Lindeboom
    Correspondence
    M.Y.A. Lindeboom, MD PhD, University Medical Center Utrecht, Department of Pediatric Surgery KE.04.140.5, PO Box 85090, 3508 AB Utrecht, The Netherlands, Tel.: +31 88 755 5555
    Affiliations
    Congenital Esophageal and Airway Team Utrecht, Department of Pediatric Surgery, Wilhelmina Children's Hospital, University Medical Center Utrecht, P.O. Box 85090, AB Utrecht 3508, the Netherlands
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  • Johannes W. Verweij
    Affiliations
    Congenital Esophageal and Airway Team Utrecht, Department of Pediatric Surgery, Wilhelmina Children's Hospital, University Medical Center Utrecht, P.O. Box 85090, AB Utrecht 3508, the Netherlands
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  • David C. van der Zee
    Affiliations
    Congenital Esophageal and Airway Team Utrecht, Department of Pediatric Surgery, Wilhelmina Children's Hospital, University Medical Center Utrecht, P.O. Box 85090, AB Utrecht 3508, the Netherlands
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  • Stefaan H.A.J. Tytgat
    Affiliations
    Congenital Esophageal and Airway Team Utrecht, Department of Pediatric Surgery, Wilhelmina Children's Hospital, University Medical Center Utrecht, P.O. Box 85090, AB Utrecht 3508, the Netherlands
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Open AccessPublished:May 19, 2021DOI:https://doi.org/10.1016/j.jpedsurg.2021.05.001

      Abstract

      Background

      Thoracoscopic external traction technique (TTT) is a relatively new surgical intervention for patients with long-gap esophageal atresia (LGEA) that preserves the native esophagus. The major accomplishment with TTT is that esophageal repair can be achieved within days after birth.
      This study evaluates the childhood outcome in LGEA patients treated with TTT, including gastrointestinal outcome, nutritional status and Health-Related Quality of Life (HRQoL).

      Methods

      A cohort study including all LGEA patients that underwent TTT between 2006-2017 was conducted. Patients and/or their parents were invited to fill out questionnaires regarding reflux symptoms and HRQoL.

      Results

      TTT was successful in 11/13 patients (85%). Esophageal anastomosis was accomplished at a median age of 12 days (range 7-138), first oral feeding was started at a median of 16 days postoperatively (range 5-37). All patients required multiple dilatations and 10 patients required anti-reflux surgery.
      At median follow-up of seven years, five patients reported mild and one moderate reflux complaints. All patients but one reached age-appropriate oral diet. Most patients (80%) were within normal growth range. Overall HRQoL was comparable to healthy controls.

      Conclusion

      TTT provides acceptable results in childhood. Oral feeding can be started as soon as two weeks postoperatively. Almost all patients are able to eat an age-appropriate oral diet. Overall HRQoL was comparable to healthy controls.

      Keywords

      Abbreviations:

      DPA (delayed primary anastomosis), EA (esophageal atresia), FOIS (functional oral intake scale), GER (gastroesophageal reflux), HRQoL (Health-Related Quality of Life), LGEA (long-gap esophageal atresia), TTT (thoracoscopic external traction technique)

      Introduction

      Long-gap esophageal atresia (LGEA) is a rare and complex type of esophageal atresia (EA) and accounts for approximately 10% of all newborns with EA [
      • Sfeir R.
      • Michaud L.
      • Sharma D.
      • Richard F.
      • Gottrand F.
      National esophageal atresia register.
      ,
      • Zani A.
      • Cobellis G.
      • Wolinska J.
      • Chiu P.P.L.
      • Pierro A.
      Preservation of native esophagus in infants with pure esophageal atresia has good long-term outcomes despite significant postoperative morbidity.
      ,
      • Spitz L.
      Oesophageal atresia.
      ]. In literature the definition of LGEA is inconsistent. Recently, however, the International Network of Esophageal Atresia (INoEA) has defined LGEA as “any esophageal atresia without abdominal air”, corresponding to Gross type A and B [
      • van der Zee D.C.
      • Bagolan P.
      • Faure C.
      • Gottrand F.
      • Jennings R.
      • Laberge J.M.
      • et al.
      Position paper of INoEA working group on long-gap esophageal atresia: for better care.
      ].
      Bridging the wide gap in LGEA remains a challenge for pediatric surgeons [
      • van der Zee D.C.
      • Gallo G.
      • Tytgat SHA.
      Thoracoscopic traction technique in long gap esophageal atresia: entering a new era.
      ] and several surgical approaches have been described. Esophageal repair can be performed by esophageal replacement (e.g. jejunal or colon interposition or by gastric pull-up [
      • Bax N.M.A.
      • van der Zee DC.
      Jejunal pedicle grafts for reconstruction of the esophagus in children.
      ,
      • Sherman C.D.
      • Waterston D.
      Oesophageal reconstruction in children using intrathoracic colon.
      ,
      • Spitz L.
      Gastric transposition for esophageal substitution in children.
      ]). However, most surgeons agree that the native esophagus is the best esophagus [
      • Bagolan P.
      • Iacobelli B.D.
      • De Angelis P.
      • Federici Di Abriola G.
      • Laviani R.
      • Trucchi A.
      • et al.
      Long gap esophageal atresia and esophageal replacement: moving toward a separation?.
      ]. Preservation of the native esophagus can be accomplished by delayed primary anastomosis or by open or thoracoscopic traction technique [
      • Foker J.E.
      • Linden B.C.
      • Boyle E.M.
      • Marquardt C.
      Development of a true primary repair for the full spectrum of esophageal atresia.
      ,
      • van der Zee D.C.
      • Vieirra-Travassos D.
      • Kramer W.L.M.
      • Tytgat S.
      Thoracoscopic elongation of the esophagus in long gap esophageal atresia.
      ]. Delayed primary anastomosis entails that the esophagus is restored two to three months after birth [
      • Friedmacher F.
      • Puri P.
      Delayed primary anastomosis for management of long-gap esophageal atresia: a meta-analysis of complications and long-term outcome.
      ]. Prolonged delay of esophageal continuity may lead to several disadvantages, including swallowing difficulties due to postponed oral feeding and prolonged hospital stay [
      • Puri P.
      • Blake N.
      • O'Donnell B.
      • Guiney E.J.
      Delayed primary anastomosis following spontaneous growth of esophageal segments in esophageal atresia.
      ,
      • Smith I.J.
      • Beck J.
      Mechanical feeding difficulties after primary repair of oesophageal atresia.
      ,
      • Cavallaro S.
      • Pineschi A.
      • Freni G.
      • Cortese M.
      • Bardini T.
      Feeding troubles following delayed primary repair of esophageal atresia.
      ]. With the thoracoscopic external traction technique (TTT) however, as also developed by our center, esophageal repair can be accomplished within days after birth [
      • van der Zee D.C.
      • Gallo G.
      • Tytgat SHA.
      Thoracoscopic traction technique in long gap esophageal atresia: entering a new era.
      ,
      • van der Zee D.C.
      • Vieirra-Travassos D.
      • Kramer W.L.M.
      • Tytgat S.
      Thoracoscopic elongation of the esophagus in long gap esophageal atresia.
      ]. Although several studies have been conducted on the outcome after esophageal replacement and delayed primary anastomosis in LGEA, this is the first study that evaluates the childhood outcome after the TTT.
      The aim of this study is to evaluate the outcome in childhood in LGEA patients treated with TTT, including gastrointestinal outcome, nutritional status and Health-Related Quality of Life (HRQoL).

      Methods

       Study design and participants

      A retrospective cohort study was conducted including all LGEA patients corrected via the thoracoscopic external traction technique (TTT) at the University Medical Center Utrecht, Wilhelmina Children's Hospital, between 2006 and 2017. Electronic medical records were reviewed. All LGEA patients since 2006 were treated with TTT and patients were considered eligible for the study if TTT for repair of LGEA was completed. Only patients with Gross type A or B (no distal tracheoesophageal fistula) were included. Patients with a failed procedure were excluded from further analysis. Patients with Down syndrome were excluded from analysis of questionnaires.

       Surgical procedure

      Prior to surgery, a standard rigid bronchoscopy was performed in almost all EA patients to evaluate the presence of a proximal fistula and to evaluate the severity of tracheomalacia. The subsequent TTT has previously been described by Van der Zee et al., [
      • van der Zee D.C.
      • Gallo G.
      • Tytgat SHA.
      Thoracoscopic traction technique in long gap esophageal atresia: entering a new era.
      ,
      • van der Zee D.C.
      • Vieirra-Travassos D.
      • Kramer W.L.M.
      • Tytgat S.
      Thoracoscopic elongation of the esophagus in long gap esophageal atresia.
      ]. In short, thoracoscopic traction sutures were placed at both esophageal ends and were fixed externally with mosquito forceps. Approximation of the esophageal ends was evaluated by postoperative X-rays. When this approximation hampered prematurely, thoracoscopic adhesiolysis was performed. Both ends were anastomosed during a final thoracoscopic procedure. A chest tube was positioned next to the esophageal anastomosis. Initially a gastrostomy was placed for feeding, in later patients a laparoscopic gastropexy was performed to prevent the stomach from migrating into the thorax. Patients were kept on parenteral feeding during the traction period.

       Clinical assessment

      Baseline characteristics, including gender, gestational age, birthweight, type EA and associated anomalies were collected from the medical records. All patients had regular check-ups at the Wilhelmina Children's Hospital and since 2017 a multidisciplinary routine follow-up schedule (age 0 up to 17 years) had been introduced for all EA patients. Gastrointestinal and respiratory symptoms, development and health-related-quality of life parameters were assessed.

       Surgical outcome

      Surgical data, including age at surgery, traction time and gastrostomy or gastropexy placement were obtained. Postoperative data, including ventilation time, NICU and hospital length of stay, postoperative complications (i.e. leakage, stenosis) and first enteral and oral feeding were collected.

       Gastroesophageal reflux

      Validated reflux-questionnaires were used to define gastroesophageal reflux (GER). Two different questionnaires were used for evaluation of GER and dysphagia. The age-adjusted Gastroesophageal Reflux Symptom Questionnaire (GSQ) [
      • Deal L.
      • Gold B.D.
      • Gremse D.A.
      • Winter H.S.
      • Peters S.B.
      • Fraga P.D.
      • et al.
      Age-specific questionnaires distinguish GERD symptom frequency and severity in infants and young children: development and initial validation.
      ] was used for patients from 2 to 12 years old and the Reflux Disease Questionnaire (RDQ) [
      • Shaw M.J.
      • Talley N.J.
      • Beebe T.J.
      • Rockwood T.
      • Carlsson R.
      • Adlis S.
      • et al.
      Initial validation of a diagnostic questionnaire for gastroesophageal reflux disease.
      ,
      • Aanen M.C.
      • Numans M.E.
      • Weusten B.
      • Smout A.
      Diagnostic value of the reflux disease questionnaire in general practice.
      ] was used for children of 12 years and older. The GSQ-questionnaire was available as parent-proxy report and contains questions on the frequency (n) and severity of reflux and dysphagia in the past seven days, which was scored for severity on a 7-point Likert scale ranging from 1 (none) to 7 (most severe). The RDQ was available as self-report and contains questions on the frequency and severity of regurgitation, heartburn and dyspepsia in the past seven days, which were scored on a 6-point Likert scale from 0 (never/none) to 5 (daily/most severe). Symptoms for all questionnaires were divided in four categories: no symptoms, mild (mild symptoms weekly), moderate (mild symptoms daily or severe symptoms weekly) and severe symptoms (severe symptoms daily).

       Functional oral intake scale (FOIS)

      The functional oral intake scale (FOIS) was used to evaluate oral intake. It consists of a numeric scale concerning oral intake, ranging from 1 (nothing by mouth) to 7 (full oral diet, no restrictions) [
      • Crary M.A.
      • Mann G.D.C.
      • Groher ME.
      Initial psychometric assessment of a functional oral intake scale for dysphagia in stroke patients.
      ].

       Nutritional status

      Weight and height measurements were collected and converted into the weight-for-length z-score using the Netherlands Organization for Applied Scientific Research (TNO) growth standards [

      TNO Groeicalculator voor de vijfde landelijke Groeistudie. 2013. https://groeiweb.pgdata.nl/calculator.asp.

      ]. A z-score below -2SD was considered pathological [

      World Health Organization. Nutrition landscape information system (NLIS) country profile indicators: interpretation guide. 2010. https://www.who.int/nutrition/nlis_interpretation_guide.pdf.

      ,
      • IJsselstijn H.
      • Gischler S.J.
      • Toussaint L.
      • Spoel M.
      • van der Cammen-van Zijp M.H.M.
      • Tibboel D.
      Growth and development after oesophageal atresia surgery: need for long-term multidisciplinary follow-up.
      ].

       Health-related quality of life (HRQoL)

      Health-Related Quality of Life was evaluated using the age-adjusted Pediatric Quality of Life Inventory (PedsQL™) 4.0 Generic Core Scales questionnaire. Patients and/or their parents were asked to fill out this questionnaire. It encompasses the domains physical functioning, emotional functioning, social functioning and (pre-)school functioning and it was scored for frequency on a 5-point Likert scale from 0 (never) to 4 (almost always). Scores were transformed to a 0-100 scale, with a higher score representing a better HRQoL. Scores were compared to healthy controls with a total scale cut-off point score of -1SD below the population sample mean (69.7 for child self-report and 65.4 for parent-proxy report). Scores of 1 SD below the mean of the healthy population are at risk for an impaired HRQoL [

      WJ.W. Varni, T.M. Burwinkle, M. Seid, D. SkarrThe PedsQL* 4.0 as a pediatric population health measure: feasibility, reliability, and validity. vol. 3. n.d. https://doi.org/10.1367/1539-4409(2003)003<0329:TPAAPP>2.0.CO;2.

      ].

       Statistical analysis

      Nonparametric variables are presented as median and range and categorical data is presented as frequencies and percentages. Mean differences are presented with 95% confidence intervals. Data from children and their parents was treated as paired.
      The analyses were performed with SPSS for Windows, version 25.0 (IBM Corp., Armonk, NY) and R 4.0.0 (R Core Team, Auckland, New Zealand).

       Ethical approval

      This cohort study was submitted to the UMCU Ethics Committee. No ethical approval was required according to the Medical Research Involving Human Subject Act. The study was carried out in accordance with the Declaration of Helsinki. Informed consent from all patients, and/or their parent if applicable, was obtained before sending the questionnaires.

      Results

      Between 2006 and 2017, a total of 14 patients with long-gap esophageal atresia were operated in the Wilhelmina Children's Hospital. Three patients were excluded from further analysis: a primary thoracoscopic repair was feasible in one patient and the elongation procedure failed in two patients. Of the two failed patients, the traction sutures tore down in the first patient (type A) and a subsequent jejunal position was performed. The length of hospital stay was 44 days. There was no sign of leakage and the patient required no fundoplication. In the second patient (type B), the proximal pouch was perforated by the Replogle tube and a gastric pull-up was performed. This patient was premature (33 weeks) and had a concomitant anorectal malformation. The length of hospital stay was 133 days. Since TTT failed in these patients, they were not evaluated in the analysis of the follow-up. All subsequent TTT procedures since 2013 were successful.
      TTT could be completed in eleven patients, of which five (46%) were male. The median gestational age was 34+4 weeks (range 30+2-39+6) with a median birthweight of 1915 grams (range 1360-3643). Five patients (46%) had a proximal fistula (type B) and six patients (54%) had EA type A. Eight patients (73%) had associated anomalies (e.g. musculoskeletal, cardiac). Patient characteristics are presented in Table 1.
      Table 1Patient characteristics.
      Variablen = 11
      Male (n, %)5 (46%)
      Gestational age (weeks) (median, range)34+4 (range 30+2 – 39+6)
      Birthweight (g) (median, range)1915 (range 1360–3643)
      Apgar score (median, range)
      1 min7 (range 2–9)
      5 min8.5 (range 5–9)
      Gross type EA (n,%)
      Type A6 (55%)
      Type B5 (46%)
      Associated anomalies (n,%)8 (73%)
      Down's syndrome1 (9%)
      VACTERL1 (9%)
      ARM1 (9%)
      Renal1 (9%)
      Musculoskeletal3 (27%)
      Cardiac2 (18%)
      Other3 (27%)
      Tracheomalacia (n,%)6 (55%)
      EA=esophageal atresia; ARM=anorectal malformations; VACTERL=Vertebral defects, Anal atresia, Cardiac defects, Trachea-Esophageal malformation, Renal anomalies and Limb abnormalities.
      Other: microcephaly, hemangiomas, microtia, retrognathia, hearing loss

       Surgical outcome

      Traction sutures were placed at a median age of 9 days (range 2–134) and esophageal anastomosis was accomplished at a median age of 12 days (range 7–138). A definitive reconstruction was performed with two thoracoscopic procedures in four patients and with three procedures in seven patients. Four patients were transferred from either another Dutch hospital or from abroad (the child that was operated at the age of 134 days). In these four patients that were transferred from another hospital a gastrostomy had been placed before referral. At the Wilhelmina Children's Hospital only the first patient had a laparoscopic gastrostomy. In the other six patients, a TTT was performed without a gastrostomy. In four out of these six patients a laparoscopic gastropexy was performed when the traction sutures were placed, to prevent the stomach from sliding up into the chest. In the other two patients neither a gastropexy nor a gastrostomy was performed. The first patient developed a partial migration of the stomach into the thorax and a subsequent laparoscopic fundoplication was performed after 9 weeks. In the second patient, there was no tension on the distal esophageal pouch and therefore a gastropexy was not indicated.

       Postoperative outcome

      After final surgery, in which the esophagus was successfully anastomosed, patients remained at the NICU for a median time of 18 days (range 3–37) with a median ventilation time of four days (range 2-14). The median initial hospital length of stay was 47 days (range 27–170). The patient who had been admitted for 170 days, suffered from respiratory incidents due to severe tracheomalacia and needed an aortopexy and redo aortopexy. During his hospital stay, the patient also required multiple anastomotic dilatations, a fundoplication and a redo fundoplication. Postoperative leakage occurred in 5 patients (46%). All leakages were treated conservatively with chest tubes and antibiotics. Surgical outcome data is presented in Table 2.
      Table 2Surgical data.
      Variable(days)n = 11(median, range)
      Age at first surgery for EA9 (2–134)
      Age at final anastomosis12 (7–138)
      Traction days4 (2–10)
      Postoperative ventilation time4 (2–14)
      Postoperative ICU stay18 (3–37)
      LOS47 (27–170)
      EA=esophageal atresia; ICU=intensive care unit; LOS=length of hospital stay (for esophageal repair)

       Tracheomalacia

      Preoperative bronchoscopy was not performed in the first TTT patient, because it was not yet introduced as routine care for EA patients in our clinic. Six from the subsequent 10 patients were diagnosed with tracheomalacia during their evaluation of the airway with preoperative bronchoscopy.
      Two patients had severe postoperative tracheomalacia related symptoms, requiring aortopexy. One patient required thoracoscopic aortopexy at the age of 11 weeks and needed a redo thoracoscopic aortopexy at the age of 16 weeks. In the other patient a thoracoscopic aortopexy was performed at the age of 19 months.

       Early gastrointestinal outcome

      First oral feeding was started at a median of 16 days after performing the esophageal anastomosis (range 5-37). In one patient with Down syndrome with postoperative anastomotic leakage and respiratory instability, oral feeding was introduced after 37 days. All patients required multiple dilatations for anastomotic stenosis. The majority of dilatations (80%) was performed within the first year of life. A fundoplication was performed in 10 patients (91%) at a median age of 3.9 months (range 1.8-6.6 months). Six of these 10 patients required a redo fundoplication after a median of 6.3 months (range 2.9-58.7 months) (Table 3). The patient with Down syndrome later developed an esophagobronchial fistula, which was closed at the age of one year.
      Table 3Gastrointestinal outcome.
      Variablen = 11
      First enteral feeding (postoperative)3 (0-21) days
      No-gastrostomy3 (1–7) days
      Gastrostomy3 (0–21) days
      Full enteral feeding (postoperative)10 (0–27) days
      No-gastrostomy10 (5–14) days
      Gastrostomy11 (0–27) days
      First oral feeding (postoperative)16 (5–37) days
      Anastomotic leakage (n,%)5 (46%)
      Esophago-bronchial fistula1 (9%)
      No. of dilatations (n, range)6 (2-20)
      Fundoplication (n,%)10 (91%)
      Age at fundoplication (median, range)3.9 months (1.8–6.6)
      Redo fundoplication (n,%)6 (55%)
      Weight-for-height z-score (SD)-0.80 (-2.20–2.40)

       Follow-up

       Reflux symptoms

      The median age at follow-up was 7.0 years (range 3.3–13.4). Nine patients (82%) were using GER medication at time of this study. Nine out of ten subjects filled out the reflux-questionnaires (90%). Three patients (33%) reported no GER complaints, five patients (56%) reported mild complaints and one patient (11%) had moderate GER complaints. Of the patients that reported no reflux symptoms, all had a fundoplication and two a redo-fundoplication. Of the five patients that reported mild symptoms, four patients had a fundoplication of three of which also had a redo-fundoplication. The patient with moderate reflux symptoms had both a fundoplication and a redo-fundoplication.

       Oral intake

      Seven patients (70%) had no food limitations (FOIS 7), one patient had specific food limitations (difficulties with carrots and meat, FOIS 6) and one patient required special preparation of food (thickening of liquids, FOIS 5), but had no other food limitations. One patient with Down syndrome had achieved full oral intake, but had later regressed to tube-feeding with minimal attempts of oral food intake (FOIS 2).

       Growth

      Most patients had a decrease in weight-for-height z-score within the first year of life and a catch-up in the weight-for-height z-sore over time; the median weight-for-height z-score at the age of 1 year was -1.77 (range -2.89 to -0.71), compared to a median weight-for-height z-score at last follow-up of -0.80 (range -2.20 to 2.40) (n = 10). Fig. 1 shows the weight-for-height z-scores over time for all included patients.
      Fig 1
      Fig. 1Weight-for-height z-score of individual patients (n = 10). The dark blue line represents the mean weigh-for-height z-score of the whole group.
      At end of follow-up, one patient had a weight-for-height z-score below -2SD due to unknown causes. Another patient had a weight-for-height z-score above 2SD, due to a small height and a normal weight-for-age. All other patients (80%) were within normal growth range.

       12.1 Health-related quality of life

      Nine out of ten PedsQL™ 4.0 questionnaires (90%) were returned. HRQoL parent-proxy report scores for patients younger than 5 years-old were higher than the cut-off points (1SD below the mean) on all domains (Fig. 2a).
      Fig 2
      Fig. 2a. HRQoL in patients <5 years old (parent-proxy report). b. HRQoL in patients ≥5 years-old (self-report and parent-proxy report). The vertical light lines represent scores of the cut-off point of 1 SD below the mean in the healthy population.
      The mean total score in patients older than 5 years was 80.1 for parent-proxy and 80.8 for child self-report (mean difference 0.7, 95%CI -5.2-3.7). These total scores were similar to the means of healthy controls (81.3 and 82.9, respectively). Both child self-report and parent-proxy report scored lowest on the school functioning domain (median of 69 and 68 respectively, compared to 77 and 80 in healthy controls), but above the threshold of 1 SD below the mean (67 and 62, respectively). Patients scored best on the social functioning domain (93 and 88, respectively) (Fig. 2b).
      One patient scored below the PedsQL™ 4.0 total score cut-off point with a score of 63.0 on child-self report, which is 6.7 points below the score cut-off point of 69.7. His total lowered score was mainly due to a low score on the emotional and school functioning domain.

      Discussion

      This is the first study to evaluate the childhood outcome of LGEA patients treated with the thoracoscopic traction technique. TTT was successful in 11/13 patients (85%). This study shows that after TTT patients are able to initiate oral feeding as soon as 16 days after esophageal correction and almost all patients achieved an age-appropriate oral diet and growth patterns within normal range. The overall HRQoL is comparable to healthy children. This study further shows that reflux is common in LGEA patients after TTT. All patients required multiple dilatations for anastomotic stenosis and almost all patients (91%) required a fundoplication.
      Postoperative stenosis is the most frequent postoperative complication after EA repair [
      • Friedmacher F.
      • Puri P.
      Delayed primary anastomosis for management of long-gap esophageal atresia: a meta-analysis of complications and long-term outcome.
      ]. In this study, all LGEA patients needed multiple dilatations for recurrent anastomotic stenosis. A high stenosis rate in LGEA patients after TTT may be explained by the risk factors for anastomotic stenosis, including anastomotic tension, leakage and GER [
      • Chittmittrapap S.
      • Spitz L.
      • Kiely E.M.
      • Brereton RJ.
      Anastomotic stricture following repair of esophageal atresia.
      ,
      • Spitz L.
      Esophageal atresia: lessons I have learned in a 40-year experience.
      ,
      • Spitz L.
      • Kiely E.
      • Brereton RJ.
      Esophageal atresia: five year experience with 148 cases.
      ,
      • Serhal L.
      • Gottrand F.
      • Sfeir R.
      • Guimber D.
      • Devos P.
      • Bonnevalle M.
      • et al.
      Anastomotic stricture after surgical repair of esophageal atresia: frequency, risk factors, and efficacy of esophageal bougie dilatations.
      ]. All patients needed multiple dilatations. Most dilatations (80%) were performed within the first year of life.
      EA patients have a greater risk of developing GER and this is especially common in LGEA patients. It has been reported in 66-88% of LGEA patients after delayed primary anastomosis (DPA) [
      • Burjonrappa S.
      • Thiboutot E.
      • Castilloux J.
      • St-Vil D.
      Type a esophageal atresia: a critical review of management strategies at a single center.
      ,
      • Sri Paran T.
      • Decaluwe D.
      • Corbally M.
      • Puri P.
      Long-term results of delayed primary anastomosis for pure oesophageal atresia: A 27-year follow up.
      ]. This is in line with our findings, in which GER symptoms were reported in 67%.
      In this study, esophageal anastomosis was performed at a median age of 12 days. Oral feeding could be started 16 days postoperatively. In delayed primary anastomosis, the anastomosis is usually performed at the age of two to three months [
      • Friedmacher F.
      • Puri P.
      Delayed primary anastomosis for management of long-gap esophageal atresia: a meta-analysis of complications and long-term outcome.
      ]. Therefore, oral feeding can only be introduced thereafter and patients will be fed by a gastrostomy in the period before esophageal anastomosis [
      • Friedmacher F.
      • Puri P.
      Delayed primary anastomosis for management of long-gap esophageal atresia: a meta-analysis of complications and long-term outcome.
      ]. Feeding difficulties are common in EA patients and include eating slowly, food refusal and choking [
      • Puntis J.W.L.
      • Ritson D.G.
      • Holden C.E.
      • Buick RG.
      Growth and feeding problems after repair of oesophageal atresia.
      ,
      • Menzies J.
      • Hughes J.
      • Leach S.
      • Belessis Y.
      • Krishnan U.
      Prevalence of malnutrition and feeding difficulties in children with esophageal atresia.
      ,
      • Mahoney L.
      • Rosen R.
      Feeding problems and their underlying mechanisms in the esophageal atresia-tracheoesophageal fistula patient.
      ]. Since infants develop their feeding and swallowing skills within the first two years of life, later introduction of oral feeding may lead to delayed positive oral experiences [
      • Bevilacqua F.
      • Ragni B.
      • Conforti A.
      • Gentile S.
      • Zaccara A.
      • Dotta A.
      • et al.
      Fixed the gap, solved the problem? Eating skills in esophageal atresia patients at 3 years.
      ,
      • Conforti A.
      • Valfré L.
      • Falbo M.
      • Bagolan P.
      • Cerchiari A.
      Feeding and swallowing disorders in esophageal atresia patients: a review of a critical issue.
      ]. Consequently, later introduction of an oral diet may impair the development of adequate feeding and swallowing skills [
      • Conforti A.
      • Valfré L.
      • Falbo M.
      • Bagolan P.
      • Cerchiari A.
      Feeding and swallowing disorders in esophageal atresia patients: a review of a critical issue.
      ,
      • Delaney A.L.
      • Arvedson JC.
      Development of swallowing and feeding: prenatal through first year of life.
      ]. Cavallaro et al. [
      • Cavallaro S.
      • Pineschi A.
      • Freni G.
      • Cortese M.
      • Bardini T.
      Feeding troubles following delayed primary repair of esophageal atresia.
      ] reported severe feeding problems after DPA in five patients compared to no feeding problems in 20 EA-TEF patients. Bevilacqua et al. [
      • Bevilacqua F.
      • Ragni B.
      • Conforti A.
      • Gentile S.
      • Zaccara A.
      • Dotta A.
      • et al.
      Fixed the gap, solved the problem? Eating skills in esophageal atresia patients at 3 years.
      ] showed that LGEA was associated with not reaching self-feeding at the age of 3 years. This is in contrast to our study, showing that almost all patients achieved an age-appropriate oral diet. Therefore, early introduction of oral feeding seems to be an advantage of TTT compared to DPA. We believe early oral feeding may contribute to patients´ oral feeding performance and reduces the long term feeding difficulties that are common in LGEA patients.
      Moreover, due to an early esophageal anastomosis (median day 12), patients do not require a preoperative gastrostomy, which may be associated with a high complication rate [
      • Kimble R.M.
      • Harding J.E.
      • Kolbe A.
      The vulnerable stomach in babies born with pure oesophageal atresia.
      ].
      The total hospital length of stay is subsequently shorter in TTT compared to DPA (47 days vs. 120-150 days) [
      • Burjonrappa S.
      • Thiboutot E.
      • Castilloux J.
      • St-Vil D.
      Type a esophageal atresia: a critical review of management strategies at a single center.
      ,
      • Sri Paran T.
      • Decaluwe D.
      • Corbally M.
      • Puri P.
      Long-term results of delayed primary anastomosis for pure oesophageal atresia: A 27-year follow up.
      ].
      Previous studies have reported that EA patients are at risk for growth problems, especially within the first years of life [
      • IJsselstijn H.
      • Gischler S.J.
      • Toussaint L.
      • Spoel M.
      • van der Cammen-van Zijp M.H.M.
      • Tibboel D.
      Growth and development after oesophageal atresia surgery: need for long-term multidisciplinary follow-up.
      ,
      • Chetcuti P.
      • Phelan PD.
      Gastrointestinal morbidity and growth after repair of oesophageal atresia and tracheo-oesophageal fistula.
      ,
      • Gischler S.J.
      • van der Cammen-van Zijp M.H.M.
      • Mazer P.
      • Madern G.C.
      • Bax N.M.A.
      • de Jongste J.C.
      • et al.
      A prospective comparative evaluation of persistent respiratory morbidity in esophageal atresia and congenital diaphragmatic hernia survivors.
      ]. This is in line with our findings, which showed a decrease in weight-for-height z-scores within the first year of life. However, a catch-up in weight-for-height z-scores was seen over time. Almost all children were within normal growth range (-2SD and 2SD) at end of follow-up, although nutritional status in most children was still below the population mean.
      In line with our findings, Peetsold et al. [
      • Peetsold M.
      • Heij H.
      • Deurloo J.
      • Gemke R.
      Health-related quality of life and its determinants in children and adolescents born with oesophageal atresia.
      ] reported a similar HRQoL in EA patients compared to healthy controls. Dingemann et al. [
      • Dingemann C.
      • Meyer A.
      • Kircher G.
      • Boemers T.M.
      • Vaske B.
      • Till H.
      • et al.
      Long-term health-related quality of life after complex and/or complicated esophageal atresia in adults and children registered in a German patient support group.
      ] studied HRQoL in complex and complicated EA, including DPA, and showed a HRQoL comparable to healthy controls. Legrand et al. [
      • Legrand C.
      • Michaud L.
      • Salleron J.
      • Neut D.
      • Sfeir R.
      • Thumerelle C.
      • et al.
      Long-term outcome of children with oesophageal atresia type III.
      ] reported that the QoL in EA patients is lower compared to healthy controls, but higher compared to patients with other chronic diseases. Our study shows that the overall HRQoL is comparable to healthy controls.
      The main limitation of this study is the small sample size, which makes statistical comparison to healthy controls impossible. However, LGEA is a rare anomaly and only patients older than two years of age that had pure LGEA (Gross type A and B) were included. Ideally, a prospective multicenter study should be conducted to increase the sample size and to evaluate and compare the long-term outcome of the different techniques used for esophageal repair in LGEA. However, since the rarity of this disease, it might proof to be very difficult to conduct such a prospective study.
      A second limitation of this study entails the wide study period, in which we changed from paper records into digital records, therefore some data could not be included (duration of parental nutrition, durations central venous catheter dependency).
      In conclusion, TTT was successful in 13 of 15 patients (85%). Major advantages of the TTT are preservation of the native esophagus, early introduction of oral feeding and a shorter total hospital length of stay. Almost all patients are able to eat an age-appropriate oral diet and have a growth pattern within normal ranges. Feeding problems later in life may be prevented by TTT. Overall HRQoL in LGEA patients treated with TTT is comparable to healthy controls.

      Declarations of Competing Interest

      None

      Funding

      This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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