An inlet patch (IP) is an area of heterotopic gastric mucosa located in the proximal esophagus. If an IP is suspected during an endoscopic examination, histological analysis is required to confirm the diagnosis. In a postmortem study in 1941, Rector et al (1) described the IP in children for the first time. An IP is present in 0.3% to 10% of adults undergoing esophageal endoscopy, and some complications related to an IP have been reported (2–5). The prevalence of IP in children is unknown, and only a few studies have addressed this issue in the pediatric population (1,6–9). The aim of this retrospective study was to assess the clinical significance, endoscopic and histological characteristics, and natural history of IP in children.
PATIENTS AND METHODS
This was a retrospective multicenter study. All patients younger than 18 years with a confirmed IP (endoscopic lesion confirmed by histological analysis of esophagus biopsies) treated during the last 10 years in 7 tertiary French pediatric gastrointestinal (GI) centers were included.
The following characteristics were noted from the medical files and endoscopic and histological reports: sex, age at diagnosis, personal medical and surgical history, including food allergy, gastroesophageal reflux disease (GERD), asthma, and repeated ear, nose, and throat (ENT) infections (>2/month). Clinical symptoms at the time of endoscopy were also noted including digestive (dysphagia, food impaction, vomiting, abdominal pain, and pyrosis), respiratory (dyspnea, cough, and false passage), and ENT (hoarseness, halitosis, and drooling) symptoms. We collected information from endoscopy (IP description: color, size, limitation, localization, and number of lesions) and histological analysis of biopsies of the IP and other parts of the upper GI tract. Biopsies were examined for the presence of heterotopic gastric mucosa, chronic inflammation, Helicobacter pylori, and eosinophilic infiltration (>15 eosinophils per high-power field). The results of pH monitoring, esophagogastroduodenal opacification, and esophagus manometry (when performed) were recorded. Information about the treatment initiated after endoscopy was recorded and included the type of drug (proton pump inhibitor [PPI], corticosteroid, or H2-receptor antagonist) and duration of treatment. The evolution of the IP and follow-up were assessed by recording the efficacy of treatment (total or partial cure), relapse when treatment was stopped, and complications related to the IP (hematemesis, esophageal stenosis, perforation, cancer) at the final follow-up.
An IP was suspected at endoscopy in 20 patients from 7 centers and was confirmed histologically in 15 children (8 boys). The median age at diagnosis was 9.5 years (range 3.3–15 years).
Eleven of the 15 children had underlying digestive disorders. Nine children had GERD, 5 had esophageal atresia, 1 had celiac disease, and 1 had a familial adenomatous polyposis (Table 1). Six patients had associated asthma or ENT involving repeated infections or atopic dermatitis linked to food allergy. In 6 children, GERD or atopic susceptibility were isolated. Fundoplication had been performed previously in 5 patients: 3 with esophageal atresia, 1 with diaphragmatic hernia, and 1 for isolated GERD. Only 1 child was asymptomatic (patient 2, a 15-year-old girl who had endoscopy for screening of a familial adenomatous polyposis), whereas dysphagia and food impaction were noted in 11 children. Other digestive symptoms were vomiting (n = 7), pyrosis (n = 4), odynophagia (n = 2), and epigastric pain (n = 3). Five children had cough, 2 had aspiration, and 3 had halitosis and drooling (Table 2).
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.
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