Endoscopy was performed in 13 patients for abdominal pain, dysphagia, food impaction, or pyrosis, in 1 patient for celiac disease workup, and in 1 patient for systematic examination of the upper GI tract in the context of familial adenomatous polyposis (asymptomatic patient). In 2 patients, eosinophilic esophagitis was suspected because of a diagnosis of food impaction, and 3 other children were assessed for the presence of complicated GERD (ENT infections, asthma).
In all of the cases, the IP was identified as a salmon-pink lesion located just below the upper esophageal sphincter, 12 to 18 cm from the front incisor teeth. The IP averaged 2 to 3 cm in diameter and were well demarcated from the surrounding pearly white normal esophageal mucosa (Fig. 1). In most IP, the surface was flat. The IP was single in 12 patients and double in 3. Fungal esophagitis was suspected in 1 child and gastritis in another. In 4 children, eosinophilic esophagitis was suspected because of white patches of the esophagus. Five children had esophageal atresia; 1 had moderate stenosis at the site of the anastomosis, but no fistula recurrence was found.
Biopsies were obtained of each IP lesion and of the distal esophageal or gastric mucosa in 13 patients. Heterotopic gastric mucosa was observed in all cases: 10 fundic type (Fig. 2), 1 antral type, and 4 both type. Mild-to-moderate chronic inflammation was found consistently. Two cases were associated with H pylori infection at the IP site (patients 5 and 10), but not at the gastric site. Candida esophagitis was confirmed in patient 15. Less than 15 eosinophils per high-power field were observed in biopsies of the median and distal esophagus from 6 children. The only pathological finding of the antrum was gastritis due to H pylori infection in 2 other patients (patients 1 and 11).
In 14 patients, including the asymptomatic child, PPI treatment was initiated for a mean duration of 4.7 months (range 1–12 months) (Table 3). One symptomatic patient (patient 6) did not receive PPI because the IP was considered an incidental finding. In 9 patients, treatment was still in progress at the time of the study. Gastric H pylori eradication treatment comprising amoxicillin and clarithromycin was given with PPI (patients 1 and 11) for 1 week.
The mean follow-up duration was 9.1 months (range 1–20 months). The natural history could not be determined in 5 patients: 2 because of a complicated history (patients 4 and 13), 2 who were lost to follow-up (patients 5 and 11), and 1 whose symptoms disappeared after fundoplication (patient 8). Although patient 6 did not receive PPI treatment, digestive symptoms disappeared, but the respiratory symptoms (cough, hyperresponsiveness) remained unchanged despite inhaled corticosteroids and antileukotriene treatment. Of the remaining 8 patients, PPI treatment was effective in 5 children whose symptoms disappeared completely (patients 1, 3, 7, 9, and 15), and the symptoms improved in 3 others (patients 10, 12, and 14). The children reported that dysphagia, food impaction, and pyrosis were less severe and occurred less frequently. Two patients reported recurrence of symptoms 1 to 7 months after PPI discontinuation. Mild hematemesis was reported by 1 patient (patient 10). No other complication related to IP (perforation, stenosis, and dysplasia) was recorded at follow-up. In 5 children (patients 2, 3, 4, 6, and 13) posttherapy endoscopic evaluation was performed after 1 to 8 months' PPI treatment discontinuation. In all cases, IP was still identified with moderate inflammation.
Our retrospective study suggests that IP is more than likely underrecognized because of its location, often neglected during esophagus exploration. The endoscopic and histological characteristics we observed are consistent with those previously reported (8–12). However, few studies have been performed in children (1,6–9), and the clinical relevance and outcome remain to be determined in children. Our study is the first to bring information about history, demographics, and outcome of patients after treatment. We also reported digestive, respiratory, and ENT symptoms with more details than in previous studies. Our data suggest that an IP can induce digestive and supraesophageal symptoms, which disappear with PPI treatment.
In prospective studies of adults, the IP prevalence ranges from 0.3% to 10%, with a mean of 3% (2,10–13). Maconi et al (14) reported a prevalence of 0.29% when the operator was unaware of the condition versus 2.27% when the operator was aware, suggesting that IPs are underrecognized during regular endoscopy.
In this study, which included 7 experienced pediatric GI centers that performed 250 to 500 upper GI endoscopy procedures each year, only 15 IP lesions were recorded in children during the last 10 years. This corresponds to an estimated IP prevalence of 0.03% to 0.05%, much lower than 5.9% that was found in a prospective study of upper GI endoscopy results in 407 children (8). This low number confirms the underrecognition of this pathology, which has received little attention in pediatric gastroenterology textbooks and manuals. Pediatric GI must be aware of the possible existence of an IP in children. To avoid missing an IP, using adequate sedation, the endoscopist must withdraw the endoscope slowly with moderate inflation while rotating the instrument, both on the way in and the way out.
Data from 2 old pediatric postmortem studies suggest that the IP frequency could be even higher, for example, 21% and 34% (7,9). In necropsy studies, the histological examination includes the entire esophagus and can detect small lesions that are not visible with endoscopy.
IP etiopathology remains poorly understood. Like Barrett esophagus, some authors have suggested that the IP is an acquired pathology and others consider the IP to be a remnant of a congenital malformation (9,10,15,16). An IP and Barrett esophagus are associated frequently in adults (20%–30% of all cases) (13,15). IP may be associated with other congenital malformations such as esophageal atresia, even if the embryologic origin differs. Emery et al (7) reported a higher IP frequency in children with a history of esophageal atresia (34%), similar to what we observed in 5 patients. De La Hunt et al (6) suggested that an IP can induce spasm, ulceration, or stricture at the site of the anastomosis, which could have significant implications for clinical management. In our study, the 5 children with esophageal atresia complained of dysphagia or food impaction without any esophageal stricture, even if it was not possible to prove the role of an IP in their symptoms. Children with esophageal atresia have many reasons to undergo repeated endoscopy, which may increase the chance of an IP diagnosis.
Little is known about the clinical significance of an IP. Although most patients are asymptomatic (2,10,13), some may have digestive or supraesophageal symptoms (2,6,8,10,12,13,17). Macha et al (8) demonstrated a higher incidence of respiratory symptoms in children with IP (especially wheezing, asthma, and cough) than in a control group, and Poyrazoglu et al (12) reported a higher incidence of dysphagia in adults with an IP. It has been argued that acid secretion plays a significant role in symptom progression. Treatment with H2-receptor antagonists or PPI is usually effective (12). In another study, the incidence of upper esophageal or laryngopharyngeal symptoms did not differ between case and control groups (10). The clinical manifestations probably depend on the size of the IP (2,12,17,18). This agrees with the physiology because the acid secreted by a small IP would be neutralized by saliva (5,19).
In our patients, except for 1 asymptomatic child, all of the patients reported dysphagia, food impaction, pyrosis, hyperresponsiveness, or repeated ENT infections. The self-reported location of dysphagia and food impaction was clearly in the upper part of the neck in some patients, and the symptoms improved dramatically after PPI treatment in most patients. Although this was not a placebo-controlled study and we cannot eliminate the possibility that PPI also improved the associated GERD suspected in some patients, our results suggest that an IP is responsible for digestive and respiratory symptoms in children. Despite no correlation between size, number, or inflammation degree of IP and symptoms, intensity has been already established, posttherapy endoscopic evaluation could help to assess IP evolution after treatment, showing reduction of the size of the IP and reduction of inflammation.
Dysphagia and food impaction are the main symptoms reported for both an IP and eosinophilic esophagitis, which are being reported increasingly in children (20). Our results showed that eosinophilic esophagitis is not associated with an IP and suggest the need for careful examination of the upper part of the esophagus to eliminate the presence of an IP in children undergoing upper GI endoscopy for suspected eosinophilic esophagitis.
There are no standardized treatment strategies for an IP. Von Rahden et al (5) proposed a clinicopathological classification that tailors the treatment and is based on the limited present literature. Asymptomatic patients (stage I) require neither specific therapy nor endoscopic surveillance. In our study, most of the patients were in stage II (esophageal or laryngopharyngeal symptoms) and required medical therapy. Complications seem to be rare especially in children (ie, there are no reports) and may be linked to acid secretion within the patches (esophageal perforation (4), stenosis (2), and malignant progression (3,5)). We reported only 1 case of hematemesis that could be linked to IP; however, the number of patients was low and the follow-up period was short. Large prospective studies should be undertaken in children to assess the long-term outcome.
The prevalence of an IP is probably underestimated, especially in the pediatric population because of limited present knowledge. Although it can be an incidental finding and may be overlooked, an IP may be the cause of digestive and respiratory symptoms, which respond to PPI treatment. Our data argue for a careful upper esophagus exploration in any child undergoing upper GI endoscopy specially for dysphagia, food impaction, or chronic cough.
The authors would like to thank Dr E. Leteurtre (Pôle de Pathologie, Centre de Biologie Pathologie, CHRU de Lille, France) for the micrograph of the lesion.
1. Rector LE, Connerly MI. Aberrant mucosa in the oesophagus infants and children. Arch Pathol Lab Med 1941; 31:285–294.
2. Borhan-Manesh F, Farnum JB. Incidence of heterotopic gastric mucosa in the upper oesophagus. Gut 1991; 32:968–972.
3. Klaase JM, Lemaire LC, Rauws EA, et al
. Heterotopic gastric mucosa of the cervical esophagus: a case of high-grade dysplasia treated with argon plasma coagulation and a case of adenocarcinoma. Gastrointest Endosc 2001; 53:101–104.
4. Sanchez-Pernaute A, Hernando F, Diez-Valladares L, et al
. Heterotopic gastric mucosa in the upper esophagus (“inlet patch”): a rare cause of esophageal perforation. Am J Gastroenterol 1999; 94:3047–3050.
5. von Rahden BH, Stein HJ, Becker K, et al
. Heterotopic gastric mucosa of the esophagus: literature-review and proposal of a clinicopathologic classification. Am J Gastroenterol 2004; 99:543–551.
6. De La Hunt MN, Jackson CR, Wright C. Heterotopic gastric mucosa in the upper esophagus after repair of atresia. J Pediatr Surg 2002; 37:E14.
7. Emery JL, Haddadin AJ. Gastric-type epithelium in the upper esophageal pouch in children with tracheoesophageal fistula. J Pediatr Surg 1971; 6:449–453.
8. Macha S, Reddy S, Rabah R, et al
. Inlet patch: heterotopic gastric mucosa-another contributor to supraesophageal symptoms? J Pediatr 2005; 147:379–382.
9. Variend S, Howat AJ. Upper oesophageal gastric heterotopia: a prospective necropsy study in children. J Clin Pathol 1988; 41:742–745.
10. Akbayir N, Alkim C, Erdem L, et al
. Heterotopic gastric mucosa in the cervical esophagus (inlet patch): endoscopic prevalence, histological and clinical characteristics. J Gastroenterol Hepatol 2004; 19:891–896.
11. Gutierrez O, Akamatsu T, Cardona H, et al
. Helicobacter pylori
and hetertopic gastric mucosa in the upper esophagus (the inlet patch). Am J Gastroenterol 2003; 98:1266–1270.
12. Poyrazoglu OK, Bahcecioglu IH, Dagli AF, et al
. Heterotopic gastric mucosa (inlet patch): endoscopic prevalence, histopathological, demographical and clinical characteristics. Int J Clin Pract 2009; 63:287–291.
13. Tang P, McKinley MJ, Sporrer M, et al
. Inlet patch: prevalence, histologic type, and association with esophagitis, Barrett esophagus, and antritis. Arch Pathol Lab Med 2004; 128:444–447.
14. Maconi G, Pace F, Vago L, et al. Prevalence and clinical features of heterotopic gastric mucosa in the upper oesophagus (inlet patch). Eur J Gastroenterol Hepatol
15. Avidan B, Sonnenberg A, Chejfec G, et al
. Is there a link between cervical inlet patch and Barrett's esophagus? Gastrointest Endosc 2001; 53:717–721.
16. Hassal E. Barrett's esophagus: congenital or acquired? Am J Gastroenterol 1993; 88:819–824.
17. Byrne M, Sheehan K, Kay E, et al
. Symptomatic ulceration of an acid-producing oesophageal inlet patch colonized by Helicobacter pylori
. Endoscopy 2002; 34:514.
18. Galan AR, Katzka DA, Castell DO. Acid secretion from an esophageal inlet patch demonstrated by ambulatory pH monitoring. Gastroenterology 1998; 115:1574–1576.
19. Jabbari M, Goresky CA, Lough J, et al
. The inlet patch: heterotopic gastric mucosa in the upper esophagus. Gastroenterology 1985; 89:352–356.
20. Attwood SE. Lamb CA. Eosinophilic esophagitis and other non-reflux inflammatory conditions of the esophagus: diagnostic, imaging and management. Best Pract Res Clin Gastroenterol
Keywords:Copyright 2011 by ESPGHAN and NASPGHAN
children; esophageal atresia; gastroesophageal reflux; inlet patch; proton pump inhibitors