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Original Articles: Gastroenterology

Characterization of Esophageal Motility in Children With Operated Esophageal Atresia Using High-resolution Impedance Manometry and Pressure Flow Analysis

Courbette, Olivier; Omari, Taher; Aspirot, Ann‡,§; Faure, Christophe∗,§

Author Information
Journal of Pediatric Gastroenterology and Nutrition: September 2020 - Volume 71 - Issue 3 - p 304-309
doi: 10.1097/MPG.0000000000002806

Abstract

What Is Known

  • Dysphagia is frequent after esophageal atresia repair.
  • Esophageal peristaltic motor pattern is always abnormal after esophageal atresia repair.
  • Esophageal dysmotility can lead to peptic esophagitis, metaplasia, or eosinophilic esophagitis.

What Is New

  • Symptoms of dysphagia are not associated with the bolus clearance.
  • The presence of residual distal contractions is associated with a more efficient bolus propulsion.
  • Contractile segment impedance is lower in patients with esophageal atresia as compared to controls and there is a trend toward an association between histopathology and contractile segment impedance of <800 ohm.

Esophageal atresia (EA) is a common congenital malformation, occurring in 1 in 2500 to 3000 live births, for which prognosis has drastically changed over the past 4 decades (1). A major concern in patients with EA is the esophageal dysmotility and its consequences. Clinically, esophageal dysmotility can lead to dysphagia symptoms but there is a lack of correlation between the severity of the dysmotility and the symptoms (2). Esophageal dysmotility also exacerbates gastroesophageal reflux disease by increasing the mucosal exposure time to gastric juice (2–4).

High-resolution esophageal manometry (HREM), the criterion standard, has allowed describing the esophageal motor patterns in children and adults operated for EA (2,3,5–8). Aside from the description of the motor patterns, however, encountered in these patients (aperistalsis, pressurization, remnant distal esophageal contractions (2)), HREM does not provide any direct information on efficacy of bolus transport mechanisms. Recently, pressure flow analysis (PFA) has been developed to allow for an integrated analysis of manometrically recorded esophageal motility and impedance recorded bolus flow (9). This method provides additional physiological insights, defining bolus flow and has been found valuable in the postfundoplication setting (10) and for investigation of nonobstructive dysphagia (11,12).

Therefore, the main aim of the present study was to use high-resolution impedance manometry (HRIM) with PFA to characterize and describe the motility patterns of the esophagus in children who have been operated for EA and to compare these with non-EA patient controls. The second aim is to test whether there is a correlation between PFA parameters and symptoms or endoscopic/histologic findings.

METHODS

Patient Selection and Data Collection

Patients

HRIM recordings of pediatric patients <18 years were extracted from a database of studies conducted in the Motility Laboratory of the Division of Pediatric Gastroenterology at the Centre Hospitalier Universitaire Sainte-Justine between December 2016 and May 2019. All EA patient studies were included. A chart review was conducted, and the following data were collected: demographic (sex, date of birth), medical history (type of EA, presence/absence of anastomotic leak or stricture), surgical history (fundoplication) and upper gastrointestinal endoscopy and pathology results (reflux esophagitis [eosinophil count <15/high power field], eosinophilic esophagitis [eosinophil count >15/high power field], gastric, or intestinal metaplasia) before HRIM study.

Symptomatology at the time of HRIM (upper gastrointestinal symptoms including gastroesophageal reflux symptoms, swallowing difficulties with different food textures, alimentary behavior changes) was evaluated through a self-assessment questionnaire systematically completed by the child or his primary caregiver and a dysphagia score was calculated according to Dakkak and Bennett (13).

Controls

Age and sex-matched patients, investigated concurrently and who had a normal motility according to Chicago classification (14) were included as controls. In all of these cases, manometry results did not lead to treatment changes.

High-resolution Esophageal Impedance Manometry

HRIM was performed with a standardized procedure, in an outpatient setting after a 4-hour fast. The procedure was conducted without sedation in all patients, with the child placed in a 30° incline position. A 4.2 mm diameter catheter (36 channels with 12 pressure sensing points/channel, each channel 1-cm apart and 18 adjoining impedance segments, each 1-cm apart; Sierra Scientific Instruments, Los Angeles, CA) was inserted transnasally after local anesthesia until the most distal recording site was positioned in the stomach. Time was allowed for the patient to accommodate to the catheter. Once the tracing had stabilized, stomach, diaphragm, lower esophageal sphincter (LES), and upper esophageal sphincter (UES) positions were determined. Saline liquid boluses (5.0 mL) were administered by syringe every 30 seconds. Optimally 10 wet swallows were recorded; however, this depended on the capacity and collaboration of the patient.

High-resolution Impedance Manometry Analysis

Esophageal pressure topography data were derived using the ManoView ESO Analysis software version 3.0 (Sierra Scientific Instruments). All tracings were reviewed and analyzed by a pediatric gastroenterologist (O.C.) under the supervision of a pediatric neurogastroenterologist (C.F.). Swallowing onset was determined by the onset of UES relaxation. LES tone and relaxation were then evaluated; mean residual pressure and 4 seconds of integrated relaxation pressure of the LES following swallowing and basal pressure were also measured. The dominant characteristics of the esophageal contraction after swallows were described after generating isobaric contour plots at a 30-mmHg threshold pressure, which has been demonstrated to be the minimum pressure associated with complete bolus transit. Patients were classified according to their main peristaltic propagation pattern whereby aperistalsis was defined as complete absence of contraction of the distal esophagus with or without pan-pressurization. Pan-pressurization pattern was identified when pressurization of the entire esophageal body was observed following UES relaxation. The patients were also subdivided into 2 groups according to the Chicago Classification 3.0 definition of “Ineffective Esophageal Motility” (14): group A with presence of distal contraction in ≥50% of the swallows and group B with the presence of distal contractions in <50% of the swallows.

Pressure Flow Analysis

During analysis, the patient characteristics were unknown to the investigator. To perform PFA, raw pressure-impedance data for the entire study was exported from the recording system in text format (.txt) and then uploaded and analyzed using purposed designed software (AIMplot software deployed via the open access Swallow Gateway application on www.swallowgateway.com). To operate esophageal AIMplot, the observer defines 6 space-time landmarks on a standard Clouse plot of the esophageal bolus swallow. Guided by these landmarks, AIMplot then automatically derives 4 categories of esophageal pressure-flow metrics: intrabolus distension pressure during bolus accommodation, during compartmentalized transport and during esophageal emptying, bolus clearance based on impedance ratio (IR) (a higher IR indicates less effective bolus clearance), bolus flow latencies based on pressure and impedance recordings at the contractile deceleration point (luminal clearance is defined by 50% recovery of impedance relative to baseline), pressure generation during luminal closure. Ramping pressure is defined as the mean gradient of pressure change during closure (mmHg/s).

The distal contractile integral (DCI) is an index of contractile vigor calculated as the product of amplitude, duration, and span of the distal esophageal contraction (mmHg · cm · s). The integrity of the proximal contractile segment is assessed by the proximal contractile integral (PCI), defined as the product of length, time, and amplitude of the proximal contraction (mmHg · cm · s). The velocity of the contraction in the lower part of the esophagus is assessed by the distal contractile velocity (DCV). Flow resistance between UES and transition zone is measured with distension pressure accommodation (mmHg) and flow resistance between the transition zone and LES is measured with distension pressure compartmentalized transport. Contractile segment impedance (CSI), the impedance value at the peak of the esophageal contraction and at a location 5 cm proximal of the esophagogastric junction is suggested as a marker of mucosal integrity.

Statistical Analysis

Descriptive data are expressed as median and interquartile range (IQR). N values represent the number of subjects included in the dataset. Comparisons between the patients with EA and the controls used the Student t test or Mann Whitney U test to compare means or medians, respectively and the Fisher exact test for count data. To determine the association between CSI threshold and histological findings, sensitivity, specificity, and Fisher exact test were calculated for each relevant threshold. The correlation between the IR and the dysphagia score was calculated by using the nonparametrical Pearson rank correlation test. Level of statistical significance was set at P = 0.05.

Ethics

The study project was approved by the research ethics committee of the Centre Hospitalier Universitaire Sainte Justine (2020–2036: Atresie HRM PFA).

RESULTS

Patients

Sixteen children with EA (6 girls; median age 11 years, IQR 6.5–12.5, range 5–17) were enrolled in the study. Fourteen (88%) had a type C, 1 (6%) a type A, and 1 (6%) a type D EA. Three (19%) had an anastomotic leak, 4 (25%) had undergone a fundoplication surgery and 4 (25%) had a history of anastomotic stricture. The median number of swallows analyzed by patient was 10 (IQR 10–10). No prokinetics were used during the HRIM studies. All patients with EA underwent an esophagoscopy with esophageal biopsies (median number 4, IQR 2–4) before the HRIM study (median time 7.1 months, IQR 5.8–13.8). Biopsies were taken at least in the distal and proximal esophagus. Macroscopically, esophagoscopy was abnormal in 5 (esophagitis n = 3; endoscopic Barrett esophagus n = 2). Abnormal histological findings were found in 7: reflux esophagitis (n = 3), eosinophilic esophagitis (n = 2), and intestinal metaplasia in 2 (Supplemental Table 1, Supplemental Digital Content, https://links.lww.com/MPG/B857). All patients reported symptoms and 50% reported dysphagia. Symptoms are reported in Supplemental Table 2 (Supplemental Digital Content, https://links.lww.com/MPG/B857).

Controls

Thirteen age- and sex-matched patient controls (6 girls, median age 14.5 years, IQR 10–16.5 range 5.75–17, P > 0.05 vs patients with EA) were included. The reason for referral was dysphagia (n = 8), chronic vomiting (n = 4), and rumination syndrome (n = 1). Esophagoscopy was previously performed in 11 (85%) of them and was normal including the biopsies.

Esophageal Motility

All patients with EA exhibited an abnormal esophageal peristaltic pattern. Visual analysis of HRIM tracings allowed to identify previously reported esophageal motility patterns: aperistalsis was noted in 4 (25%) associated with pressurization in 3 and presence of distal contractions in 12 (75%). Among the latter group, 8 presented distal contractions in ≥50% of swallows and 4 in <50% of swallows. Control subjects had normal esophageal motility according to Chicago classification (14).

Table 1 displays HRIM findings in patients and controls. In patients with EA, the PCI was significantly lower than that in controls. In patients for whom distal contractions were present, the DCI was significantly lower than that in controls. DL was similar in both groups, whereas DCV was significantly lower in EA than in controls. Basal LES pressure, as well as EGJ 4s integrated relaxation pressure, was similar in EA and controls.

T1
TABLE 1:
High-resolution impedance manometry and pressure flow analysis parameters in patients and controls

Pressure Flow Analysis

PFA data in patients with EA and controls are reported in Table 1.

Impedance Ratio

The IR was significantly higher in EA (median 0.47, IQR 0.38–0.55) compared to the control subjects (median 0.22, IQR 0.19–0.26) (P < 0.001) (Fig. 1). In order to further characterize the bolus transport in EA and to test the hypothesis that the presence of residual distal contractions is associated with a more efficient bolus propulsion, patients with EA were subdivided into 2 groups: group A with presence of distal contraction in ≥50% of the swallows (n = 8) and group B with the presence of distal contractions in <50% of the swallows (n = 8, including the patients with aperistalsis). IR was higher in group B versus group A with, respectively 0.54 (0.49–0.58) and 0.36 (0.31–0.44) (P < 0.001) (Table 2).

F1
FIGURE 1:
Impedance ratio in EA patients and control subjects. Individual values are shown and, for each group, the horizontal bar represents the median value of each population with interquartile and 5% to 95% ranges. The impedance ratio is higher in patients with EA than in control children (P = 0.002). EA = esophageal atresia.
T2
TABLE 2:
Pressure flow analysis variables in children with esophageal atresia with presence of distal contractions in ≥50% of swallows (group A) and presence of distal contractions in <50% of swallows (group B)

Contractile Segment Impedance

In the 12 patients for whom the CSI was measurable (ie, presence of distal contractions), there was a significant difference between patients with EA (median 778 Ohms, IQR 638–1229) and control subjects (median 1528 Ohms, IQR 1152–2063) (P < 0.01).

Symptoms and Pathology Findings According to Bolus Transport

Symptoms were similarly reported regardless of the presence of contractions and the score of dysphagia was not correlated to IR (Fig. 2). Histopathological findings similarly occurred whether or not distal contractions were present. Sensitivity, specificity, and Fisher exact test were determined for all relevant CSI threshold (Supplemental Table 3, Supplemental Digital Content, https://links.lww.com/MPG/B857). A CSI <800 Ohm predicted presence of histopathological findings with sensitivity: 80%, specificity: 57%.

F2
FIGURE 2:
Correlation between impedance ratio and Dakkak score using the nonparametrical Pearson rank correlation test. No score >15 was obtained.

DISCUSSION

This study reports the characterization of esophageal motility and evaluation of function using HRIM and PFA in 16 EA pediatric patients, compared to age and sex-matched control subjects. We show that esophageal dysmotility, present in all patients with EA, is associated with alteration of the bolus clearance as demonstrated by a higher IR than controls. Furthermore, we show that effective bolus transit depends on the preservation of the distal contractions of the esophageal body. Our results also suggest that CSI, when measurable, could be lower in presence of histopathological esophageal findings.

It is well known that patients with operated EA have esophageal dysmotility. Esophageal motility has been assessed in children and adults with EA by either esophageal manometry (water perfused (4,15–20) or high-resolution solid state (2,3,5–8)), impedancemetry (8,21), or videofluoroscopy (22,23). Here we confirm that all patients had an abnormal motor pattern in the body of the esophagus (aperistalsis with or without pressurization and distal contractions) with a normal LES. We show that, compared to sex- and age-matched controls, the proximal and the distal esophagus are affected in EA as suggested by the lower proximal and distal constractile integrals which reflect the strength of esophageal motility respectively above and below the anastomosis. The lower DCV in patients with EA could be the result of the esophageal motor disorganization (24). The abnormal PCI may be related to the distension of the upper esophagus above the anastomosis, whereas the abnormal DCI could be explained by abnormal development of the esophageal muscle and intrinsic innervation. Whether the dysmotility could be worsened by the surgery during repair and postoperative complications (leaks, fibrotic scars) remains unclear (25).

In the present study, PFA provided further insight into the functional consequences of the dysmotility by measuring the IR reflecting the importance of bolus residual during swallow (26). Our results confirm that the capacity of propagation of a bolus through the esophagus is severely impaired in patients with EA. We also show that the alteration of bolus flow progression is associated with the presence of the remnant distal contractions, the more preserved they are, the better the bolus clearance. This suggests that IR is a reliable marker allowing quantification of the extent of bolus transport failure associated with esophageal dysmotility that could explain the origin symptoms and complications after EA repair. Unfortunately, the present study was not sufficiently powered to demonstrate a significant association between clinical symptoms described by patients and IR values.

CSI, which integrates the impedance measurement during lumen occlusive contraction, may allow a more specific assessment of mucosal impedance in the context of EA. We found that CSI is significantly lower in the group of patients with EA compared to controls and could be more likely <800 ohm in presence of a histological complication in patients with EA. Mucosal impedance measurement has been recently demonstrated as a biomarker of esophageal mucosal integrity (27–29) of peptic esophagitis (30,31) and of active eosinophilic esophagitis (32). Many patients with EA, however, have absent motility and CSI is therefore often unreliable to interpret in this setting.

Our study has several strengths and limitations. We studied 16 well-characterized patients with EA for whom data on symptoms and endoscopy were available. We also designed a case-control study and recruited age- and sex-matched patient controls to compare the HRIM and PFA data obtained in the patients. For evident ethical reasons, we were not able to recruit healthy pediatric subjects. We had a relatively low number of patients included and the median gap between esophagoscopy and HRIM was 7.1 months. We cannot exclude that the lack of association between IR and symptoms and/or histological findings was due to a type 2 error. It is also possible that the sensitivity of the Dakkak score is not enough to finely characterize the clinical symptoms of the patients with EA. Concerning the control population, 2 of 13 patients did not undergo an esophagoscopy. Another limitation is that the HRIM studies were only performed in a 30° incline position with saline bolus swallows. Studying the patients in an upright position with viscous or solid swallows would probably add further information and potentially more sensitive measurements.

In conclusion, PFA allows further characterization of esophageal motility and bolus clearance in patients with EA. Bolus transport is severely altered in patients with EA, and the presence of residual distal contractions is associated with more efficient bolus propulsion. Symptoms were not correlated to PFA parameters and so, to the severity of the motor dysfunction. A low CSI may predict histopathological findings of the esophagus. Therefore, characterization of esophageal motility after EA repair using pressure flow analysis, as carried out in this study with a limited number of patients, provides no additional information that is useful for management of newly diagnosed patients. Whether all these findings are associated with a better outcome warrant further studies in larger cohorts.

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Keywords:

children; dysphagia; esophageal atresia; high-resolution impedance manometry; pressure flow analysis

Supplemental Digital Content

Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition