*Cincinnati Children's Hospital Medical Center, Division of Gastroenterology, Hepatology and Nutrition, USA
†the Children's Hospital of Philadelphia, Division of Gastroenterology, Hepatology and Nutrition, USA
‡Division of Allergy and Immunology, USA
§Division of Nephrology, USA
||Department of Pathology, Cincinnati, OH, USA
¶University of Pennsylvania, Clinical Center for Epidemiology and Biostatistics, Philadelphia, PA, USA.
Received 20 March, 2009
Accepted 23 December, 2009
Address correspondence and reprint requests to James P. Franciosi, MD, MS, MSCE, Cincinnati Children's Hospital Medical Center, Division of Gastroenterology, Hepatology and Nutrition, 3333 Burnet Ave, ML 2010, Cincinnati, OH 45229 (e-mail: firstname.lastname@example.org).
The present study was supported by a grant from NIH T32-DK007740, “Clinical Epidemiology Training in Gastroenterology.”
The authors report no conflicts of interest.
The field of pediatric gastroenterology has experienced rapid growth since its inception in the 1960s. Pediatric gastroenterology is now an American Board of Pediatrics–certified subspecialty that emerged from earlier training of pediatricians in adult gastroenterology units and an increased recognition of gastrointestinal (GI) disorders that are unique to children. During the last 30 years, there has been a proliferation of pediatric gastroenterologists from a few select centers around the world to an ever-growing specialty that has approximately 1 pediatric gastroenterologist per 100,000 children in the United States (1). With the development of a subspecialty focused on the disorders of the pediatric GI tract, new technologies were also developed to aid in diagnoses, such as pediatric esophagogastroduodenoscopy (EGD).
Pediatric EGD began in the 1970s and, during a 30-year period, has evolved from an infrequent procedure in the operating room with a single ocular for viewing the intestinal lining to a routine outpatient procedure using intravenous sedation and large viewing screens (2).
In parallel with the growth of pediatric gastroenterology, disorders that require EGD for diagnosis have shown a rising incidence of diagnosis (3). This increasing incidence may be due in part to changing endoscopy practices during this time period. Therefore, we hypothesized that subjects in earlier years would have a higher disease severity compared to subjects in more recent years. The aim of this study was to identify differences in subject characteristics and endoscopic practices among subjects undergoing endoscopy in 1985, 1995, and 2005.
MATERIALS AND METHODS
The Children's Hospital of Philadelphia was the first pediatric hospital in the nation, and represents the largest pediatric hospital in the 9-county greater Philadelphia area. The population catchment area serving the Children's Hospital of Philadelphia was geographically defined as Philadelphia, Bucks, Chester, Delaware, Montgomery, Burlington, Camden, Gloucester, and Mercer counties.
We conducted a retrospective analysis of children and adolescents who underwent EGD at a single center during the calendar years 1985, 1995, and 2005. All of the patients undergoing EGD with biopsy at the Children's Hospital of Philadelphia during the study time periods were identified through a systematic review of a pathology database comprising paper and electronic records. The samples were limited to subjects undergoing first-time EGD with biopsy. Subject demographics (age, sex, and race) were available for all of the subjects undergoing first-time EGD in 1985, 1995, and 2005 (4,5).
Additional data regarding clinical presentation and details of the EGD procedure were obtained through abstraction of the medical records in a random sample of 100 subjects undergoing first-time EGD in 1985, 1995, and 2005 (sample command; STATA 9.0, StataCorp, College Station, TX). Inpatient and outpatient medical records were available in 78, 84, and 83 subjects at the 1985, 1995, and 2005 time points, respectively.
A severity index for indications for EGD was created as a dichotomous variable of high versus low severity. Components indicative of high severity included any of the following documented before EGD: a diagnosis of failure to thrive, GI bleeding, severe systemic disease, abnormal upper gastrointestinal (UGI) radiographic findings, and abnormal screening laboratory results. Severe systemic disease included conditions such as malignancy, genetic syndromes, systemic inflammatory conditions, or conditions requiring hospitalization in the intensive care unit. Abnormal UGI radiographic findings were defined as documentation of stricture, ulceration, or mass. Abnormal screening laboratories included elevation of inflammatory markers, hemoglobin values of less than 10.5 mg/dL, abnormal celiac serologies, abnormal inflammatory bowel disease (IBD) serologies, and an albumin of less than 3.5 mg/dL. Additional data included medications at the time of the EGD. Data abstraction was confined to these defined endpoints because of the limited data available in 1985 subject charts.
The EGD procedure characteristics included the anatomic biopsy sites and the number of biopsies obtained at each site. A complete EGD was defined as a study that included biopsies from the esophagus, stomach, and duodenum. The presence of any abnormalities on visual inspection was noted, as well as the histological results.
Statistical analyses were conducted using STATA 9.0 (StataCorp) and Pass 2005 (NCSS, Kaysville, UT). Descriptive statistics for subject characteristics and basic demographics were reported as means and standard deviations or medians with ranges depending on the variable distributions. Subject characteristics and EGD practices were compared across time points using ANOVA test for normally distributed variables, Krushal-Wallis tests for non-normally distributed variables, and χ2 test for dichotomous outcome variables. All of the tests were considered significant at the P < 0.05 level. This study was approved by the Children's Hospital of Philadelphia institutional review board.
The number of first-time and total EGDs in the time points of 1985, 1995, and 2005 are summarized in Figure 1 and Table 1. Given that the number of children and adolescents in the greater Philadelphia catchment area was stable during this interval, the first-time EGD rate increased 12-fold (from 7.9 to 95.2 procedures per 100,000 children per year) during this 20-year interval (P < 0.001) (Table 1). During the same interval, the number of pediatric gastroenterologists and outpatient gastroenterology clinic visits also increased significantly.
Patient demographics in subjects undergoing first-time EGD with biopsy in the time points of 1985, 1995, and 2005 are summarized in Table 2. Data are provided for the entire population of children undergoing EGD with biopsy in each of the 3 years, as well as the random subsamples of 78, 84, and 83 subjects in 1985, 1995, and 2005, respectively. The age, sex, and race distributions in the total sample and the subsamples within each of the 3 eras are comparable, confirming that the random subsamples are representative of the entire populations in each era. The distributions of sex and race were not significantly different across the 3 eras. However, the proportion of subjects that were younger than 1 year of age decreased significantly from 1995 to 2005 within the total population (P < 0.001) and the random subsample (P < 0.005).
The clinical presentations, indications for EGD, and disease severity in the subsamples were compared across the 3 eras (Table 3). The proportion of subjects with GI bleeding declined significantly from 34% to 5% during the 3 eras (P < 0.001). In contrast, the proportions with abdominal pain increased from 23% to 43% (P < 0.01). The proportion of subjects with a high severity index for indications for EGD decreased significantly during the 3 eras (P < 0.005), as summarized in Figure 2.
Acid-suppression medication–prescribing practices before EGD were also examined. Histamine 2 receptor antagonists medications or proton pump inhibitors were prescribed before EGD in 14.1% of subjects in 1985, 35.7% of subjects in 1995, and 55.4% of subjects in 2005 (P < 0.001). In the respective years, proton pump inhibitors alone were prescribed in 1.3%, 4.8%, and 41.0% of subjects undergoing first-time EGD (P < 0.001).
EGD practices and findings changed significantly from 1985 to 2005 as summarized in Table 4. A complete EGD (with biopsies obtained in the esophagus, stomach, and duodenum) was performed in 17.7% of EGDs in 1985, 79.8% in 1995, and 95.2% in 2005 (P < 0.001). The proportion of biopsies with histologic abnormalities declined from 1985 to 2005 at each site. Finally, the number of esophageal biopsies obtained during each EGD procedure increased significantly during the 3 eras (P < 0.001) (Fig. 3). In 1985, 53.2% had 2 or more esophageal biopsies compared to 97.3% in 1995 and 98.8% in 2005.
This study of children undergoing first-time EGDs with biopsy in the years 1985, 1995, and 2005 demonstrated significant differences in subject characteristics and endoscopy practices. Children who underwent EGD in 1985 were less likely to have isolated abdominal pain, were more likely to have upper GI bleeding, and had a higher disease severity index compared to subjects in 1995 and 2005. These findings support the hypothesis that the indications for pediatric EGD have changed during the last 20 years.
In the earlier years, pediatric EGD was a new technology and pediatric gastroenterology was a developing field. The differences in absolute numbers of first-time EGDs, EGDs per population, and EGDs per GI attending support the concepts of relative inexperience with pediatric endoscopy, lower number of referrals from general pediatricians, and the use of other diagnostic modalities such as pH probes, manometry, and Crosby capsules between 1985 and the later years. High disease severity and GI bleeding rates in the earlier years may also have been influenced by acid-suppression medication–prescribing practices and improvements in the management of diseases that predispose to GI bleeding, such as liver transplantation for portal hypertension–associated variceal bleeding. In addition, the numbers of EGDs performed by pediatric gastroenterologists and by outpatient gastroenterology clinic visits were comparable in 1995 and 2005. This suggests that the overall increases in EGD rates were related to increases in the number of gastroenterologists, outpatient gastroenterology visits, referrals from pediatricians, and education about disorders diagnosed with EGD in recent years.
In 1996, the North American Society of Pediatric Gastroenterology stated, “Diagnostic upper endoscopy is generally not indicated for uncomplicated gastroesophageal reflux [or] uncomplicated functional abdominal pain” (6). In other words, children with uncomplicated gastroesophageal reflux disease (GERD), who were likely to be treated with acid suppression therapy, were not undergoing routine EGD in 1985 and 1995. In 2001, the North American Society for Pediatric Gastroenterology guidelines for the management of symptoms of gastroesophageal reflux recommended a trial of acid suppression therapy before endoscopy (7). These statements imply that the practice of EGD in children has shifted from a procedure seldom performed in the setting of low-severity indications, such as uncomplicated GERD, to 1 routinely performed after a trial of acid suppression therapy to exclude other etiologies. Our data support the clinical application of these practice parameters, with more children having lower disease severity undergoing EGD with biopsy in the later years. Of particular interest in these data is the higher proportion of infants undergoing EGD in 1995 compared to 1985 and 2005. It is postulated that infants were less likely to undergo EGD in 1985 given the technical limitations and physician inexperience with EGD in this age group. However, with increasing physician experience in 1995, the proportion of infants undergoing EGD increased. In 2005, although the absolute number of infants undergoing EGD remained approximately the same compared to 1995, the 2-fold increase in total first-time EGD procedures decreased the relative proportion of this age group. This suggests that although the increasing experience of pediatric endoscopists performing infant EGD is reflected in the rise of infant EGDs from 1985 to 1995, the use of acid suppression therapy in this age group likely contributed to a decreased proportion of infants undergoing EGD from 1995 to 2005.
In addition to improved technology and physician's technical experience, there have been new discoveries and interest in pediatric GI inflammatory disorders that may also influence the number of EGDs performed. In particular, in the last decade, eosinophilic esophagitis (EoE) has received considerable attention as a “new” disease, with the first consensus report being published in 2007. EoE is a disorder that requires EGD with biopsy for diagnosis and is defined by lack of response to gastric acid–suppression medications. In a cohort of 381 children with EoE, 82% (312) were subclassified into a gastroesophageal reflux category, of whom 61% (191) were described as having epigastric pain, heartburn, or water brash (8). Subjects presenting with isolated epigastric abdominal pain, heartburn, water brash, nausea, and vomiting would be classified as having a low symptom severity index in our study. Therefore, EoE subjects with a low symptom severity index may have been underdetected in the earlier years. Furthermore, the recognition of EoE as a distinct clinical entity from GERD and functional abdominal pain has increased the use of pediatric EGD in the 2005 era relative to 1985 and 1995 as an important diagnostic modality for a disorder that cannot be diagnosed by any other means. Therefore, EGD practices may serve as an important confounding variable in the description of rising EoE incidence rates.
Changing indications for pediatric endoscopy during this 20-year period may have also influenced other disease detection rates such as that of IBD. In a prospective study in 2000 to 2001, Kugathasan and colleagues reported pediatric population–based IBD incidence rates with a higher proportion of children with Crohn disease than had been reported previously (9–11). Practices of routine EGD evaluation in conjunction with total colonoscopy with ileal intubation during the initial evaluation for IBD were not commonly practiced until the 1990s. IBD disease detection rates may be confounded by the changing practices of pediatric EGD.
Celiac disease is another important pediatric GI disorder for which endoscopy is the gold standard to establish the diagnosis. In the United States, Olmsted County, MN, described a 51-year experience of the diagnosis of celiac disease across all ages in their population after having an endoscopic biopsy to establish the diagnosis (3). They report respective annual incidence rates of celiac disease with a dramatic rise from 0.9/100,000 in 1950 to 1989, 3.3/100,000 in the 1990s, and 9.1/100,000 in 2000–2001 (3,12–16). In another study, serologic testing across a random sample of 4126 subjects from the US population from 1996 to 2001 estimated a prevalence of celiac disease in subjects without risk factors to be as high as 1:133 (0.8%) (15). Fasano (13) has described this phenomenon as an iceberg effect. Subjects with severe symptomatic disease who are likely to go to their physician, be referred to a gastroenterologist, and have their diagnosis of celiac disease confirmed with EGD represent only a small fraction of the true population with milder or even asymptomatic (latent) disease.
In addition to changing patient characteristics described in our study, changing EGD practices also serve as a confounding variable in the description of rising incidence rates. In our study, 46.8% of subjects in 1985 had 0 or 1 esophageal biopsies compared to 2.4% in 1995 and 1.2% in 2005. Only 19.0% of subjects in 1985 had 3 or more esophageal biopsies taken compared to 52.4% in 1995 and 38.5% in 2005 (P < 0.001). Gonsalves et al (17) have shown previously that the sensitivity of detecting EoE is dependent upon the number of esophageal biopsies taken at the time of diagnosis. If only 1 biopsy is taken, the sensitivity is 55%, compared to 94% if 4 or more biopsies are taken. The fewer number of esophageal biopsies taken in the earlier years may have underestimated the true incidence and prevalence of this disorder.
This study of children undergoing first-time EGDs in the years 1985, 1995, and 2005 supports the hypothesis that the subject characteristics and EGD practices among children undergoing EGD have changed during the last 20 years. In the context of a 12-fold rise in the number of EGDs performed from 1985 to 2005, it is not surprising that subjects with the highest disease severity would undergo EGD in 1985 relative to 2005. Because of the patient characteristics and endoscopic practices among those subjects who undergo EGD change, disease detection rates will also change. Therefore, caution must be exercised in reporting increasing incidence of disease rates when these disease rates may instead reflect increasing rates of diagnosis of disease rather than true increase in disease occurrence.
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