A cohort study was conducted including all LGEA patients ≥ 16 years old who had undergone JI or GPU at the University Medical Center Utrecht (UMCU) and the University Medical Center Groningen between 1985 and 2003. As of 2018, all 17-year-old EA patients are routinely referred to the gastroenterologist for clinical assessment and endoscopic and histologic screening for esophageal mucosal lesions. All adult LGEA patients (> 17 years), that were not yet included in the routine follow-up, were invited for screening. Patients that had ER for LGEA underwent an one-time barium contrast study, to evaluate the anatomy of the graft. Data was collected prospectively. Gastroscopies that were performed after the age of 17 years and within the last four years, were reviewed retrospectively.

All ERs had been performed by experienced pediatric surgeons. The GPU was performed as previously described by Spitz et al[11,24]. In short, after mobilization of the stomach and a pyloromyotomy transhiatal posterior mediastinal tunnel is created and the stomach is transposed into the thorax through the esophageal hiatus. Thereafter, the proximal esophagus and the apex of the stomach are anastomosed in the neck. JI was performed as described in these studies[12,25,26]. The pedicle graft is created: The jejunum is transected close to Treitz ligament and at the level of the third mesenteric artery branch. The uppermost part of the graft is tunneled into the right chest, behind the stomach and through the posterior part of the hiatus. Thereafter, two anastomosis are performed, one between the proximal esophagus and the jejunal graft and another between the distal esophagus and the jejunal graft.

Baseline characteristics, including gender, age, type of EA and associated anomalies were obtained from the electronic medical records.

Gastro-intestinal symptoms: Gastrointestinal symptom assessment (e.g., reflux, dysphagia) was derived from the routine outpatient follow-up at the Gastroenterology Department.

Contrast study: Upper gastrointestinal barium contrast studies were analyzed by an experienced radiologist and pediatric surgeon for the following parameters: Anastomotic stenosis, stasis of contrast, reflux, graft-dilatation and graft-lengthening (resulting in a siphon shaped graft) of the JI and the position of the stomach in GPU patients.

Upper endoscopy and histology: Upper endoscopy was performed by a gastroenterologist to assess the esophagus, the anastomotic site(s), the grafts, the gastroesophageal junction and the stomach. Reflux esophagitis and intestinal metaplasia were scored according to the Los Angeles (LA) classification[27] and Prague criteria[28]. Barrett’s esophagus was defined as columnar lined esophagus on endoscopy in combination with intestinal metaplasia on histology. In patients with JI, biopsies were taken from both the distal and proximal esophagus. Jejunal grafts were evaluated on proximal or distal stenosis, (distal) dilatation of the graft and on macroscopic lesions. Biopsies of the jejunal graft were taken if mucosal abnormalities were present. The GPU was evaluated on anastomotic stenosis, macroscopic lesions and altered anatomy. In patients with GPU, biopsies were taken just proximal to the anastomosis. In case of macroscopic abnormalities of the GPU, biopsies were taken. Endoscopies were reviewed by an experienced gastroenterologist and a pediatric surgeon. Biopsies were evaluated for inflammation, eosinophilia and metaplasia by the Pathology Department by an expert gastrointestinal pathologist.

This study was part of a larger cohort study on the long-term outcome in LGEA patients. The study protocol was submitted to the UMCU Ethics Committee (METC 18-458/C). According to the Medical Research Involving Human Subject Act, no ethical approval was required.

Continuous skewed variables were presented as median and range, categorical data were presented as frequencies and percentage. Group differences between JI and GPU patients, and associations between different outcome measures were assessed using the Fisher’s exact test for bivariate variables and the Mann-Whitney U-test for continuous variables. Differences with a P value < 0.05 were considered statistically significant. The analyses were performed using SPSS for Windows, version 25.0 (IBM Corp., Armonk, NY).

Reflux complaints were reported in six of the nine GPU patients (67%) and in four out of 11 JI patients (36%) (P = 0.37). Dysphagia symptoms were scored in seven JI patients (64%) vs two GPU patients (22%) (P = 0.09). Three GPU patients (33%) experienced severe feeding problems. Due to swallowing disabilities, one patient was still fully dependent on jejunostomy feeding, with minimal attempts of liquid oral feeds. Another patient required additional jejunostomy feeding until the age of 21 years, but has recently reached a full oral diet. One patient required additional drink nutrition to achieve a full oral diet. In the JI group, no severe feeding problems were observed.

The median body mass index (BMI) of JI patients was 20.9 kg/m² (range 17.9-27.6) vs 19.5 kg/m² (range 17.5-21.6) in GPU patients (P = 0.08). Two JI patients (18%) were underweight (BMI < 18.5 kg/m²) and one patient was overweight (BMI > 25 kg/m²) (Table 3). Three GPU patients (33%) were underweight, none of the patients were overweight.

GPU: Barium contrast studies were performed in five of the nine GPU patients (56%). In one patient, the stomach was completely transposed into the thorax. This patient showed some lengthening of the distal esophagus and stasis of liquids in the distal esophagus. Another patient, with Down syndrome, also showed stasis of contrast in the esophagus. No reflux was observed in these patients.

Four out of nine GPU patients did not undergo a contrast study; three patients did not consent because they did not experience major gastro-intestinal complaints. One patient with mental retardation was unable to perform a contrast study due to severe swallowing difficulties.

JI: Barium contrast studies were performed in all 11 JI patients. Ten patients (91%) showed stasis of contrast in the ER graft. None of the patients had a proximal or distal stenosis. The jejunal graft was dilated in six (55%) patients. In two of these patients, graft dilatation was severe. In four of these six patients, mild to moderate lengthening of the distal part of the jejunal graft was observed (Figure 2).

Open in New Tab   Full Size Figure   Download Figure

Figure 2 Lengthening and dilatation of the distal jejunal graft.

GPU: All GPU patients (n = 9) had undergone gastroscopy. The median distance from the incisors to the anastomosis was 19 cm (range 17-24). Macroscopic anomalies of the native esophagus were seen in five patients (56%); three patients showed columnar lined esophagus (33%) (C0M2, C0M2, C1M2) (Figure 3). One patient had an erosion at the distal part of the esophagus and another patient, who was jejunostomy dependent due to severe swallowing difficulties, had a pinpoint stenosis of the anastomosis (Table 4).

Open in New Tab   Full Size Figure   Download Figure

Figure 3 Barrett’s esophagus (C0M2) in a gastric pull-up patient.

JI: All JI patients (n = 11) had undergone upper endoscopy. The median distance from the incisors to the proximal anastomosis was 21 cm (range 18-25), the median length of the jejunal graft was 15 cm (range 12-22) and the median length of the distal esophagus was 4.5 cm (range 0-8). In none of the patients a proximal or distal anastomotic stenosis was present. Macroscopic anomalies were seen in five patients (45%): Two patients showed macroscopic esophagitis of the distal esophagus according to the LA classification (grade A, n = 1; grade B, n = 1), one patient had fields of squamous epithelium in the proximal part of the jejunal graft, one patient showed elevation of normal mucosa in the distal esophagus and a neurological impaired patient had stasis of food and an ulcer at the distal part of the jejunal graft. None of the JI patients showed columnar-lined esophagus (Table 4).

GPU: In three patients with macroscopic columnar-lined esophagus, biopsies of the native distal esophagus showed intestinal metaplasia in two patients (22%), both with Prague classification C0M2 (2 men; median age 21.6 years). In two patients, biopsies of the distal esophagus showed chronic inflammation. Biopsies in another two patients showed hyperplastic squamous epithelium without dysplasia. In one patient, histopathology revealed that biopsies of cardia and corpus were obtained. Histopathology showed no signs of dysplasia in any of the patients. In one patient without macroscopic anomalies, no biopsies specimens were taken (Table 4).

JI: In three patients, histology of the native distal esophagus showed normal esophageal mucosa. In one patient, biopsy of the native distal esophagus showed a single glandular tube with signs of intestinal metaplasia. A target biopsy of a small mucosal elevation of the distal esophagus in another patient showed mild reactive changes of the mucosa. In two patients, biopsies of the stomach were obtained. Biopsies in one patient showed no abnormalities. In the other patient without macroscopic anomalies, biopsy of the stomach showed lymphoid infiltration, further investigation excluded lymphoma. None of the biopsies showed signs of esophageal dysplasia. In four patients without suspected macroscopic anomalies (36%), no biopsies specimens were taken (Table 4).

Columnar-lined esophagus of the native esophagus occurred more often in the GPU group compared to the JI-group (3 vs 0 patients, P = 0.07). No associations were found in GPU patients between reflux symptoms and macroscopic mucosal abnormalities during upper endoscopy or with intestinal metaplasia. Both patients that had confirmed intestinal metaplasia, reported reflux symptoms and were treated with proton-pump inhibitors (PPIs). No association was found between intestinal metaplasia and GER symptoms. No association was found between BMI and reflux.

Of the six patients with a dilated JI-graft, five (83%) reported dysphagia complaints. Of the four patients with lengthening of the JI-graft, three (75%) reported dysphagia symptoms. However, there was no statistically significant association between dilatation or lengthening and dysphagia.

Previously, esophageal replacement (ER) with gastric pull-up (GPU) or jejunal interposition (JI) used to be the standard treatment for long-gap esophageal atresia (LGEA). Gastrointestinal symptoms are common in EA patients and may occur even more frequently after ER, due to a change of the anatomy.

Long-term macroscopic and microscopic graft changes are currently unknown and may be clinically relevant in patients with LGEA.

This study aims to evaluate clinical symptoms and macroscopic and microscopic graft changes in adolescence and adulthood.

A cohort study including all LGEA patients ≥ 16 years who had undergone ER between 1985-2003 at two tertiary centers in the Netherlands was conducted. Clinical symptoms, contrast studies and endoscopies were collected prospectively.

Nine GPU patients and eleven JI patients were included in this study, with a median age of 21.5 years and 24.4 years respectively. Six of nine GPU patients (67%) reported reflux complaints and 64% of JI patients reported dysphagia symptoms. Dilatation of the jejunal graft was observed in 55%. Three GPU patients had columnar-lined epithelium and in two of these patients intestinal metaplasia was histologically confirmed.

Long-term follow-up revealed significant macroscopic and microscopic graft changes after ER. Furthermore, this study revealed long-term clinical symptoms after both GPU and JI. GPU patients may have an increased risk on intestinal metaplasia. Dilatation of the graft and dysphagia symptoms were present in the majority of JI patients. Follow-up during adulthood after ER for LGEA is therefore suggested.

This study highlights the importance of implementing an endoscopic follow-up program after ER for LGEA, particularly after GPU. Further investigations with larger patient cohorts are necessary to validate these findings.