High-Resolution Esophageal Manometry in Teenagers with Esophageal Atresia

Introduction: Children with surgically repaired esophageal atresia (EA) show esophageal dysmotility. Due to the performance of high-resolution manometry (HRM), three motility alteration patterns have been described, which allowed to know the segmental alterations. Objective: To describe the esophageal esophageal behavior, according to the peristaltic pattern, since there are significant differences among the groups in study.


Introduction
EA is one of the most frequent birth defects, with an incidence of 1 in 3000 live births [1]. Until the 1950s, these patients had 100% mortality; nowadays, the survival rate is greater than 90%, and only those with associated severe malformations die [1] [2] [3] [4] [5].
Type C EA (atresia of the esophageal proximal segment with tracheoesophageal fistula between the trachea and the distal segment) is the most common variant, since it is present in 85% of the cases [6] [7] [8]. There is evidence that the esophageal motor disorder present in these children is secondary to a congenital neuromuscular disorder and a postoperative disorder [9]- [14]. Patients that survive the operation have a greater risk of developing gastroesophageal reflux disease (GERD), caused by anomalies in the esophageal motility and its resulting delay in the evacuation of acid of the esophageal lumen.
There was a hypothesis that suggested that motility alteration could contribute to dysphagia and to the high prevalence of gastroesophageal reflux in these patients [15] [16] [17]. Also, there were reports of a greater incidence of severe esophagitis with requirement of fundoplication, which shows a larger failure rate [16] [17]. Esophageal dysmotility has been proved in children with EA through performance of conventional perfusion manometry.
Lemoine C. et al. described three motility alteration patterns with HRM in children with repaired EA. Said study allowed a more precise knowledge of segmental esophageal motility [18]. Currently, there are no reports exclusively made about teenagers with repaired EA that describe segmental esophageal motility with HRM.

Objective
To describe esophageal motility patterns found with HRM in teenagers with EA and to relate these with the associated esophageal pathology and its severity.

Materials and Method
Patients older than 12 years of age with corrected esophageal atresia who were being followed up in the Esophageal Atresia Committee of the Children's Hospital of La Plata, Sr. María Ludovica, Buenos Aires, Argentina, were included in the period between January 2015 and January 2016. Teenagers should be asymptomatic, with no history of esophageal blockage or dilations, during the last six months; all feeding orally. With these characteristics, 10 patients were being followed up; five patients were female, and five male. Patients who did not meet age or who were symptomatic with the need for dilation or esophageal blockage in the last six months were excluded.
We collected demographic data (age, sex, birth date), medical history (type of atresia, presence or absence of fistula, associated malformations) and surgical history (postoperative complications, antireflux procedures, esophageal dilations), and reviewed previous studies such as gastrointestinal videoendoscopy and esophageal biopsies, conventional manometry and 24-hour pH monitoring. The study has been approved by the provincial Ethics Committee.
Being a cross-sectional study, the follow-up of patients was not evaluated in relation to their underlying pathology. There was only intention to know the current status at the time of the study.
HRM Technique Patients were cited at the El Cruce Hospital in Florencio Varela, Buenos Aires, Argentina, to perform the HREM. The study was performed on an outpatient basis and patients presented with 8 hours of fasting. The procedure was conducted without sedation. The equipment used was a Sandhill Scientific Inc (Rancho, CO, USA) high-resolution manometer, with simultaneous impedance.
We used a catheter with 32 pressure sensors/16 impedance sensors, 12Fr.
The procedure started by introducing intranasal xylocaine gel. After 4 -5 minutes, we nasally introduced the catheter, asking the teenager to take swallows to ease its way to the esophagus. When the right position of the catheter was checked, according to the visual map, we gave them 10 sips of 5 mL of water to evaluate the motility during liquid deglution. Then, we performed maneuvers to provoque peristaltic strength with multiple liquid (repetitive, 2 mL each) and solid (pieces of cookies) deglutions. Once the procedure was over, which lasted 15 minutes on average, we withdrawn the catheter and ended the study.

HRM Analysis
Manometry profiles were analyzed with Bioview TM (Sandhill TM ) software (ver-  [24]. LES IRP, tone and residual pressure were also evaluated. DCI was valued and adjusted to the esophageal length, which is considered as the distance between both sphincters. Results were classified according to the three motility patterns present in children with EA described by Lemoine C. et al. Said patterns were: aperistalsis (without peristaltic wave, with or without LES abnormality), pressurization (simultaneous contraction of the entire esophageal body after deglution in at least 2 swallows) and distal contraction (contraction after deglution in at least 2 swallows in the esophageal middle or distal third) [18]. Statistical Analysis A descriptive analysis was made in a cohort of patients with repaired achalasia.

Results
Ten teenagers with surgically repaired EA were evaluated. Seven patients were girls. The median age was 15 years (12 -17 years) and all patients showed adequate growth as for weight and size. 90% showed type C atresia and only one of them had type A (EA without fistula). In addition, 50% of the patients presented associated malformations: syndactyly, sclerosis, mild neurological conditions, cardiopathies or renal diseases. No early postoperative complications were registered. However, 70% of teenagers presented late postoperative complications, such as stenosis that required dilations. Throughout their lives, 50% of the patients showed repeated broncho-obstructive features. In previous gastrointestinal videoendoscopies, 3 patients presented esophagitis (2 B and one C, according to Los Angeles classification). When evaluating 24-hour pH monitoring, we had data of 9 patients with the following results: 3 patients with normal studies (33.3%). The number of proximal episodes of gastroesophageal reflux and the clearance time of the bolus were within normal values in 100% of the teenagers. HRM Ten studies were performed with no technical difficulties. None of the patients evaluated presented a normal peristaltic pattern and these were classified according to the main peristaltic pattern observed.
We analyzed the tracings and identified 3 different esophageal motility patterns: complete aperistalsis, pressurization and distal esophageal contraction. The complete aperistalsis pattern was present in 2 patients, who showed absence of motility in the esophageal body, with or without LES anomalies. There was 1 teenager with the pressurization pattern, with alteration in the LES relaxation. According to the distal esophageal contraction pattern, we identified 7 patients.  Pressure of the LES was normal in 90% of teenagers, with a media of 28.6 mmHg and a range between 13 and 45 mmHg. The other patient presented a pressure of 77 mmHg.
Relaxation and IRP were normal in 90% of the cases. The mean was 11.6 mmHg and the range between 6 and 17 mmHg. There was only one case with increased IRP of 21 mmHg, which belonged to the pressurization group.
DCI could only be valued in patients with the distal contraction pattern; these values were below normal in 7 patients and, in 3 of them, a value of 0 mmHg/cm/sec. The other 3 patients, with DCI within normal parameters, showed a mean of 565.6 mmHg/cm/sec, with a range between 464 and 753 mmHg/cm/sec. In addition, when we observed the UES pressure, the mean value was 86.9 mmHg, with a range between 14 and 158 mmHg, and 2 cases exceeded the normal value. We also compared the three patterns and described the differences found among them (Table 1 and Table 2).
It should be noted that teenagers that showed the distal contraction pattern had normal results in esophageal endoscopies and its biopsies in 100% of the cases; however, in the pressurization and complete aperistalsis groups, patients presented severe esophagitis and required Nissen antireflux procedure in 100% of the cases. Regarding pH monitoring, 100% of the patients in these 2 groups also had pathologic results, but in the distal contraction pattern group, only 57% of the cases were pathologic.

Discussion
As mentioned in the objective of this study, we could describe the esophageal segmental alterations in teenagers with atresia through performance of high-resolution manometry and identify the presence of three the peristaltic patterns in pediatric population [25] [26] [27] already described.
Up to now, there are few publications about esophageal motility in patients with EA with HRM [18]- [30] and no studies have been made with a teenage cohort exclusively, age in which it is possible to retrospectively evaluate the evolution of the kid, and to relate him/her with the type of esophageal motility. Singendonk and collaborators compare the Chicago Classification metrics in a pediatric population [28], correlating age, esophageal length and HRM values. Due to the regression analysis, they determined that the patient's age and the shorter esophageal length had positive correlation with a greater IRP, shorter distal latency (DL) and smaller peristaltic break. Mean age was 8.9 ± 0.7 years, adjusted for diagnostic criteria. However, in our study, we used adult values, since we had a teenage population with adult size.
In our study, the esophageal motility patterns found in teenagers were identical to those described for the general pediatric population by Lemoine [18]: pressurization, aperistalsis and distal contraction. The differences among the three groups are significant, as regards the presence of GERD and the need for antireflux procedure. We could correlate the type of esophageal motility with the presence or severity of gastroesophageal reflux, but the number of patients is limited, so it is not possible to get a statistical value.
In the pressurization group we only found a patient with incomplete LES relaxation but, since he/she had had Nissen antireflux procedure, we could not determine whether this pattern is present due to a neuromuscular incoordination prior to the fundoplicature or if this is secondary to it. This doubt comes up because we do not have preoperative manometric studies. In the aperistalsis and pressurization groups, 100% of the patients had had Nissen fundoplicature, while in the distal contraction group, teenagers had never had esophagitis or Nissen fundoplicature. So, we could deduce that in the first two groups, the motor disorder is more severe, conditioning a severe reflux disease. We found no differences regarding symptomatology, according to the peristalsis pattern the patients belonged to, since they were 100% asymptomatic.
When analyzing 24-hour pH monitoring, we observed bolus clearance and normal proximal reflux episodes, independently of the motility pattern found.
Previous studies of pH monitoring in patients with EA informed that both parameters are not affected, despite the motor disorder these patients have, and there are no significant differences with the control patients' group [29] [30].
This could partly explain the absence of symptomatology, since clearance has influence on it, as Maheen Hassan refers in her work [31].

Conclusions
It remains to be established whether, according to the peristalsis pattern presented by the patient, if a prognosis of severity of gastroesophageal reflux disease can be estimated.
Taking into account that this population provides little information about symptomatology (due to its chronicity), that there are different motility patterns and that, according to the pattern, severity of the reflux could be different, these patients should be systematically studied and controlled, without waiting for the appearance of symptoms. By performing an HRM combined with pH monitoring, we can predict the future esophageal behavior and the severity of the gastroesophageal reflux, so we can avoid the performance of multiple unnecessary studies and the presence of greater complications. According to the patient's peristaltic pattern, severity of GERD could be predicted.
Even though our data shows there are significant differences among the evaluated groups, the limited number of cases only allows a descriptive statistical analysis. It is necessary to evaluate a greater number of patients to confirm our hypothesis.

Limitations of the Study
The size of the probe to perform the HREM was a limitation to select the patients' age. One patient refused to perform the pH-impedance measurement.