Introduction
Pediatric esophagogastroduodenoscopy (EGD) began in the 1970s. Parallel to the growth of pediatric gastroenterology, an increase in the use of EGD has been observed [
1]. Currently, EGD is a sensitive diagnostic tool with rare complications, which can be performed at any age [
2].
EGD in children can either be diagnostic or therapeutic. In 1996, the North American Society of Pediatric Gastroenterology and Nutrition provided general indications for diagnostic upper gastrointestinal (GI) endoscopy in infants, children, and adolescents, which included the presence of symptoms indicative of an underlying organic pathology of the gastrointestinal tract [
3]. American Society for Gastrointestinal Endoscopy (ASGE) provided modified guidelines for pediatric EGD in 2000, 2008, and 2014 [
4‐
6]. In 2015, the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) and the European Society of Gastrointestinal Endoscopy (ESGE) developed the latest guidelines for pediatric gastrointestinal endoscopy, where the indications for diagnostic EGD were clearly stated [
7].
Multiple studies have discussed the indications and diagnostic yield of EGD. Miele et al. found that nearly one-fourth of endoscopic procedures performed were inappropriate [
8]. Compliance with published guidelines is associated with improved diagnostic efficiency [
9]. A systematic review found that the diagnostic yield of appropriate endoscopies was higher than that of inappropriate ones (43.3% vs. 35.1%) [
10]. A recent retrospective study in children found that 47.2% of upper GI endoscopies revealed abnormal findings and that age < 60 months, abdominal pain, dysphagia/odynophagia, and heartburn were predictive of abnormal endoscopy findings [
11]. Another study showed that EGD was both macroscopically and histologically normal in 80.6% of cases and that unless there are alarming symptoms, younger children do not need EGD. However, studies on pediatric EGD are limited and are mostly retrospective. Based on our prior work in one center, we conducted this multicenter cross-sectional observational study to delineate the indications and diagnostic yield of EGD and depict the relationship between factors and endoscopic and histological diagnostic yields in pediatric patients who underwent their first diagnostic endoscopy.
Methods
Study design
This was a prospective, cross-sectional observational study (ClinicalTrials. gov ID: NCT03603093) in five hospitals, each in a different city in China. These centers were the Children’s Hospital of Fudan University in Shanghai, Children’s Hospital of Fudan University Xiamen Branch in Xiamen, Henan Children’s Hospital (Zhengzhou Children’s Hospital) in Zhengzhou, Wuhan Children’s Hospital in Wuhan, and Hunan Children’s Hospital in Changsha. Ethics approval was obtained from all five hospitals.
At the onset of this study, a steering committee was formed, comprising five directors of the gastroenterology department and 1–2 doctors in charge of data collection from each study center. A case report form (CRF) with inclusion and exclusion criteria, questionnaire, study definitions, and guidelines for data collection were provided to the centers. The questionnaire included the basic characteristics of the patients and indications for EGD. Professor Ying Huang and attendings in the Department of Gastroenterology in the Children’s Hospital of Fudan University designed the CRF and questionnaire based on their previous work.
Patient selection and data collection
Patients aged 0–18 years who underwent diagnostic EGD in any of the five children’s hospitals were included in our study. The indications for EGD were based on the latest guidelines by ESPGHAN and ESGE. Patients with insufficient clinical data for the study, those who could not complete the EGD examinations, and those who did not conform to the defined diagnostic indications, such as removal of foreign body and endoscopic surgery were excluded from the study.
Recruitment commenced in the five selected hospitals from December 2018 to September 2019. Of the patients who underwent EGD during this period, 2268 fulfilled the inclusion criteria and gave consent to provide data on variables in the questionnaire.
Doctors responsible for data collection administered the questionnaire either to the parents of the patients or the patients themselves. Questions were about the patient’s basic characteristics, indications for EGD, and date of EGD. In addition, endoscopic and pathologic reports were combined with the questionnaires. Biopsy was performed routinely, except in those who declined biopsy.
Indication
Indications were classified as abdominal pain, recurrent vomiting, weight loss or failure to thrive, GI bleeding, unexplained anemia, symptoms of gastroesophageal reflux (GER), diarrhea, caustic ingestion, dysphagia, etc., according to the latest guidelines by ESPGHAN and ESGE. Some patients had more than one indication.
Endoscopic and histologic findings
A positive endoscopic yield was defined as the presence of relevant findings on endoscopy, grouped into categories such as esophagitis, gastritis, duodenitis, peptic ulcer, Helicobacter pylori infection diagnosed through rapid urease test, and others. The histologic findings mainly included moderate or severe inflammation or Helicobacter pylori infection confirmed by immunohistochemical staining.
Data management
The questionnaires and endoscopic and pathologic reports from the other four centers were sent back to the center in Shanghai. Data entry was performed by two people using the EpiData software. After double entry, the data were compared; non-conforming data were confirmed by referring to the original questionnaire.
Statistical analysis
All analyses were performed using Stata 12.0 statistical software (StataCorp LP, College Station, TX, USA). Descriptive statistics were calculated for demographic features (sex and age). After generating descriptive counts and proportions for symptom variables, Chi-square tests were used to compare patients with different demographic features or symptom variables for diagnostic yield. Then, univariable and multivariable logistic analyses were performed to assess the relationship between demographic features or symptom variables and the presence of a positive endoscopic or histologic abnormality. Significance was set at p < 0.05.
Discussion
Pediatric EGD aids the understanding of the pathophysiology of common GI disorders in children and plays an important role in the management of some disorders. Parallel to the utilization of endoscopy in pediatric patients, the volume of EGD being performed has increased. When using this tool, we need to review its use to maximize its efficacy.
In this multicenter study, we found that abdominal pain was the most common indication, followed by recurrent vomiting, weight loss, GER symptoms, GI bleeding, diarrhea, and others. According to studies performed in large children’s hospitals or pediatric clinics, abdominal pain is also the most common indication for upper GI endoscopy in UK and US cohorts [
12‐
14]. A retrospective analysis (carried out over 20 years from 1985 to 2005) of children and adolescents who underwent EGD at a single center revealed that the proportion of patients with abdominal pain increased from 23 to 43%, while that of patients with GI bleeding declined from 34 to 5% over the 20-year interval [
1]. Studies in some small countries have found the most frequent indication in their centers was surveillance for esophageal varices and suspected celiac disease [
15‐
17].
Currently, guidelines provide the indications for EGD; the guidelines developed and newly modified in 2014 by ASGE provide indications for EGD [
6]. The guidelines developed in 2015 by ESPGHAN and ESGE also elaborate indications for EGD [
7]. These two guidelines have the following in common: abdominal pain, weight loss, failure to thrive, unexplained anemia, dysphagia or odynophagia, caustic ingestion, recurrent vomiting with unknown cause, GI bleeding, diarrhea/malabsorption (chronic), and intractable or chronic symptoms of GERD. However, unexplained irritability, anorexia, and suspicion of graft versus host disease differentiate them.
In previous retrospective studies, the diagnostic yield of EGD was significantly different, varying from 18.9 to 79% [
13‐
18]. Several more recent studies have identified certain basic patient characteristics including age that affect diagnostic yield. The diagnostic yield was found to be higher in teenagers [
11,
13,
14,
19] and lower in those aged < 7 years, especially in those without alarming symptoms [
20]. In this study, we found that the infant group and the teenager group appeared to have a higher yield of abnormal endoscopic and histological findings, similar to the results of previous studies [
11,
13,
14,
19].
Except for the basic characteristics, the composition of the patients in the study also affected the overall diagnostic yield, because diagnostic yield varies in patients with different indications for EGD. In our multivariate regression analyses, we observed that abdominal pain was the most common indication; however, patients with abdominal pain had a lower rate of abnormal endoscopic or histological findings than those without. This finding is similar to that of a large retrospective study of 1,000 children in 2013, in which the most common indication (abdominal pain) had lower rates of abnormal endoscopic findings (28.9%) than other indications including stricture which was confirmed on upper GI series (100%), foreign body (88%), GI bleeding (57%), dysphagia (56%), and positive celiac screening (52%) [
14]. Other studies have also shown that patients with generalized abdominal pain had a lower rate of abnormal endoscopic findings (36%) than those with UGI bleeding (71.3%), variceal surveillance (54.8%), recurrent persistent vomiting (38%), and dyspepsia (37.8%) [
17].
Our study findings can be a further supplement to the indication of abdominal pain. Our study showed that patients with indications of abdominal pain and any other symptoms (such as recurrent vomiting, weight loss or failure to thrive, GI bleeding, unexplained anemia, GER symptoms, diarrhea, caustic ingestion, and dysphagia), those with evidence of Helicobacter pylori infection before EGD, or those whose family members had Helicobacter pylori infection had higher rates of abnormal endoscopic findings. Therefore, these patients seemed to have more necessity to receive EGD.
Biopsy is often performed during diagnostic endoscopy to determine the pathology of focal lesions or identify the presence of Helicobacter pylori. The guidelines developed by ESPGHAN and ESGE in 2015 recommend routine tissue sampling even in the absence of visible endoscopic abnormalities in all children undergoing EGD. The low rate of abnormal endoscopic findings in our study may be due to the presence of mild chronic inflammation of the mucosa in most patients.
Our study has few limitations, which could be attributed to the multicenter nature of the study. Although prior training of the endoscopists and investigators were conducted regarding the methodology to ensure uniformity, heterogeneity could not be completely eliminated. Moreover, heterogeneity might also exist due to the difference in pathological diagnosis by pathologists at different centers. Hence, the indications and diagnostic yields of gastroscopy should be validated in future evidence-based studies for better patient management.
In conclusion, EGD is valuable for diagnosis in children with digestive symptoms, especially those with alarming features such as dysphagia, GI bleeding, and recurrent vomiting. Biopsy and histological examinations should be performed more aggressively in infants, those with weight loss or without abdominal pain.
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