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Original Articles: Gastroenterology

Functional Luminal Imaging Probe Assessment in Postfundoplication Patients Changes Management Beyond Manometry

Rosen, Rachel; Garza, Jose M.†,‡; Nurko, Samuel

Author Information
Journal of Pediatric Gastroenterology and Nutrition: June 2020 - Volume 70 - Issue 6 - p e119-e123
doi: 10.1097/MPG.0000000000002658
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Abstract

What Is Known

  • Children remain symptomatic after fundoplication but understanding the postfundoplication physiology is difficult.
  • High-resolution esophageal manometry with impedance is often used as the gold standard test for esophageal function after fundoplication but the test is difficult to perform and interpret in young children.

What Is New

  • Fundoplication patients had a lower esophagogastric junction distensibility using functional luminal imaging probe compared with controls.
  • Patients who responded symptomatically to an esophagogastric junction intervention had either a higher integrated relaxation pressure or a lower distensibility than patients who did not have an esophagogastric junction intervention.

Although adult patients with fundoplication-related side effects present with clear symptoms of dysphagia, gas-bloat, and early satiety, pediatric fundoplication patients, particularly young children, may often have symptoms, which are nondescript, including cough, food aversion, poor growth, and recurrent respiratory infections. Trying to determine if the fundoplication is contributing to symptoms is difficult and patients undergo multiple tests including endoscopy, impedance testing, barium imaging, and high-resolution manometry with impedance (HRIM) before deciding on an intervention. There is still no consensus in paediatrics, which test best predicts, which fundoplications are problematic, and which test best predicts esophagogastric junction (EGJ) obstruction meriting intervention.

HRIM, which is often used to assess EGJ dysfunction in adults and children, has limitations in pediatric patients including the inability for young or medically complex patients to take different textures during testing, the lack of reference values for the integrated relaxation pressure (IRP) of the lower esophageal sphincter predicting adequate bolus transit in pediatric postsurgical patients, the lack of data on the complex interrelationship between symptoms and IRP values in young children, and the difficulty reporting symptoms during testing in young, nonverbal children.

Recently, functional luminal imaging probe (FLIP) has been proposed as a new tool to measure EGJ distensibility and may shed light into postfundoplication EGJ physiology (1,2). Although small adult studies using FLIP highlight reduced EGJ distensibility in postfundoplication patients, how the reduced EGJ distensibilities impacted clinical decision-making or where FLIP falls into the diagnostic algorithm for the evaluation of the postfundoplication patient is not known (3,4). In addition, there are no studies using FLIP to assess EGJ obstruction in the pediatric population and there are no pediatric or adult studies determining the interrelationship between FLIP, HRIM and clinical decision-making or outcomes. We hypothesize that EGJ distensibility in the postfundoplication pediatric patient is decreased compared with other patient groups and may assist in clinical decision-making. It is the goal of this study to describe the fundoplication physiology using FLIP and compare EGJ distensibility to HRIM parameters and their utility in clinical decision-making and clinical outcomes.

METHODS

We performed a case control study of FLIP and HRIM in consecutive symptomatic pediatric fundoplication patients presenting to 2 large motility centers between January 2018 and November 2019. FLIP and, whenever available, HRIM results of all consecutive fundoplication patients were compared with those from control and achalasia pediatric patients. Control patients were defined as patients with a distensibility of >2.8 mm2/mmHg based on achalasia data suggesting that values below this merit intervention (5), and, whenever available, a normal IRP and esophageal motility, and symptoms that were not consistent with EGJ obstruction or any primary motility disorder. The referral diagnoses for the controls were chest pain, dysphagia, and regurgitation. Because of the ethics of performing this test in otherwise healthy patients, all control patients were symptomatic but, based on history and clinical tests including FLIP, were felt to be functional in origin. Achalasia patients included in the analysis had absent peristalsis and an IRP >15 mmHg (6).

Functional Lumen Imaging Probe Recordings

All FLIP studies of EGJ distensibility were performed under general anesthesia with propofol alone. Each patient had a FLIP curve performed (10, 15, 20, 25, and 30 mL inflations) at the EGJ. For patients older than 10 years old, additional inflations to 40, 50, and 60 mL were performed. For each inflation, balloon pressures were monitored to ensure that there were no pressures >50 mmHg. Because of a lack of data on maximum inflations in children, clinical judgement based on inflation pressures and diameter achieved determined the inflation curves. As the FLIP software provides real time numbers, the greatest distensibility seen at the largest balloon inflation was used for intraoperative decision-making. The detailed measurements outlined below were performed after the procedure using FLIP 2.0 software analysis program (Minneapolis, MN). We determined distensibility at different balloon sizes adjusted for weight, maximum pressure at the largest EGJ diameter, maximum distensibility per inflation series, maximum diameter per inflation series, maximum diameter per inflation series, and maximum diameter per inflation adjusted for weight. All of the endoscopists were motility-trained, were aware of HRIM results before FLIP, and were aware of the differences between HRIM catheters between patients.

High-resolution Manometry With Impedance

For children older than 10 years old, a 12 french catheter HRIM catheter (36 pressure sensors, 12 impedance sensors) was used (Medtronic, Minneapolis, MN) and in children <10 years old, a 6F HRIM catheter (25 pressure sensors, 12 impedance sensors) was used (Laborie, Williston, VT). A standard esophageal manometry was performed in the semi-upright position as previously described (7). Tracings were reviewed to assess IRP, percentage of failed peristalsis, and peristaltic integrity.

Interventions

Intraoperatively, patients underwent the following EGJ interventions: botulinum toxin injection (Botox) to the EGJ; dilation of the EGJ; or no EGJ intervention. In some patients, pyloric Botox was administered in addition to or in lieu of an EGJ intervention when the EGJ function was preserved. The decision to intervene was made based on symptom type and severity, HRIM results and FLIP findings. To assess success of interventions, patients were followed for a minimum of 6 months after the FLIP testing. Blinded outcome assessments were performed before analysis of FLIP to prevent bias. Symptomatic improvement was defined as complete or near complete improvement in the primary symptom for referral for the primary symptom for which the patient was referred as determined by the first clinical note after the index procedure.

Statistics

SPSS (version 24) was used for analysis (Amonk, NY). Results are expressed as mean + SD. Spearman correlations between the variables were performed as indicated. Proportions were compared using χ2. T tests were used to compare means. Nonparametric statistics were used when data was not normally distributed. Differences were considered statistically significant when P < 0.05.

The FLIP parameters mentioned above were then compared with HRIM parameters including mean IRP and incomplete versus complete bolus transit where incomplete bolus transit was defined as a swallow associated drop in impedance to >50% of baseline with failure to return to 50% of baseline in 2 or more channels after completion of the peristaltic wave.

We then determined, which HRIM and FLIP variables predicted intraoperative intervention (no intervention, EGJ intervention including Botox or dilation, or non-EGJ intervention, such as pyloric Botox) and favorable clinical outcome.

This study was approved by the Institutional Review Board at Boston Children's Hospital (IRB 00004012) and Children's Healthcare of Atlanta (STUDY00000395).

RESULTS

Twenty-one fundoplication patients, 7 control patients, and 6 achalasia patients were included in the analysis and all had FLIP testing with example tracings shown in Figure 1. Of these 34 patients, 4 control, 6 achalasia, and 16 fundoplication patients also had HRIM performed. Patient demographics are show in Table 1. As MMS makes infant-appropriate HRIM catheters, the mean age of patients (N = 6) who had an MMS study was 2.8 ± 1.7 years with a range of IRPs from 8.4 to 24 mmHg. For the remaining 10 patients, Medtronic catheters were used; the mean age of these patients was 13.9 ± 4.8 years with a range of IRPs from 4.8 to 21.4 mm Hg. There was no statistical difference of IRPs between groups (fundoplication patients, MMS: 15.1 ± 6.7 mmHg versus Medtronic: 10.8 ± 5.1 mmHg, P = 0.18).

FIGURE 1
FIGURE 1:
Examples of esophagogastric junction distensibility and motility in control (A), achalasia (B), and fundoplication (C) patients. EGJ regions are circled. In control patients, the EGJ relaxes completely (blue) compared with achalasia and fundoplication patients (red). EGJ = esophagogastric junction. EGJ = esophagogastric junction.
TABLE 1
TABLE 1:
Patient demographics

Comparisons Between Control, Achalasia, and Fundoplication Patients

Differences in distensibilities and HRIM between diagnoses are shown in Table 1. There were significant differences in maximum distensibility by diagnosis. There were also significant differences in balloon inflation curves between the 3 groups with maximum distensibility reached at lower balloon volumes for controls compared with fundoplication patients and this relationship persisted (Fig. 2). Individual patient inflation curves are shown in Figure 2; in many fundoplication patients, there is a threshold effect, such that once a certain balloon size is reached, the distensibility and EGJ diameter increase significantly. In addition, in fundoplication patients, larger balloon inflations resulted in incremental increases in esophageal diameter and distensibility unlike in achalasia patients in whom the distensibility were consistently low; overall, there was a significant positive correlation between diameter and distensibility (r = 0.73, P = 0.001). There was no significant correlation between IRP and distensibilities within groups (achalasia: r = 0.5, P = 0.2, fundoplication: r = 0.49, P = 0.07, controls: r = 0.13, P = 0.87).

FIGURE 2
FIGURE 2:
Impact of balloon size on distensibility where (A) is the balloon fill volume adjusted by weight (mL/kg) needed to generate the maximum distensibility and (B) is the distensibility curves per patients at each balloon inflation.

In fundoplication patients, there were no significant differences in the mean distensibilities in patients with normal (4.5 ± 0.8 mm2/mmHg) versus abnormal esophageal transit (3.1 ± 2.1 mm2/mmHg, P = 0.1) measured by HRIM. Similarly, there were no significant differences in the mean IRPs between patients with normal (11.8 ± 5.8 mmHg) versus abnormal transit (13.4 ± 6.5 mmHg, P = 0.6).

Fundoplication Interventions

Of the 21 fundoplication patients, 11 (52.4%) had an EGJ intervention; 7 had EGJ Botox, and 4 had EGJ dilation. In addition to the EGJ interventions, 6 patients (28%) had pyloric Botox injections; 3 patients only received pyloric Botox, and 3 received both pyloric Botox and a EGJ intervention. Seven patients (33%) had no intervention to either the EGJ or the pylorus.

We compared the mean maximum distensibility between those patients in which there was an EGJ intervention to those that did not have an intervention; patients who had an intervention had significantly lower EGJ distensibility (2.4 ± 1 mm2/mmHg) than those that did not have an EGJ intervention (4.9 ± 1.5 mm2Hg/mmHg, P = 0.001).

In the fundoplication patients, who had both FLIP and HRIM studies, there was no significant difference in the mean IRP of patients who did not have an intervention (11.3 ± 5.8 mmHg) compared with those who did have an intervention (13.9 ± 6.1 mmHg; P = 0.4). When we compared the maximum distensibilities in patients with normal versus abnormal transit by HRIM, there was a tendency for those with normal transit to have higher distensibilities (4.6 ± 0.9 mm2/mmHg) compared with those with abnormal transit (3.1 + 2.1 mm2/mmHg; P = 0.1).

Seventy percent of our patients had improvement in symptoms 6 months after FLIP measurement. When looking at only those patients who had an endoscopic intervention (N = 14), 71% of patients experienced symptomatic improvement. When looking only at those patients who had medication or diet interventions, 57% of patients had symptomatic improvement.

DISCUSSION

This is the first study using FLIP technology to study EGJ function in pediatric postfundoplication patients and the first pediatric or adult study showing that EGJ distensibility is a useful clinical tool to guide clinical management. Unlike in adult patients where the presenting symptom of EGJ obstruction is almost universally dysphagia, pediatric patients have more complex symptoms presentations and patients have associated comorbidities, which could also contribute to symptoms. Pediatric gastroenterologists are, therefore, hesitant to intervene in the postsurgical lower esophagus, either through dilation or EGJ Botox injections, for fear of worsening the symptoms for which the fundoplication was initially performed. Therefore, sensitive tests are needed before intervening.

In pediatrics, HRIM with an assessment of IRP is often used to determine if there is EGJ obstruction. However, recent studies have shown that esophageal dysfunction is more complex than a single number (8). Most recently, IRP values have been viewed in concert with bolus transit such that the presence of bolus stasis, even with a normal IRP may warrant clinical interventions, and similarly high IRPs may not merit intervention if bolus flow is normal (9,10).

FLIP may allow for a more physiologic measurement of GEJ function. Data on FLIP in postfundoplication patients is limited, and there is no data determining the interrelationship between HRIM, FLIP, and clinical decision-making. In an adult study of 10 fundoplication patients and 10 control patients who had both HRM and FLIP, the authors found that there was poor correlation between EGJ compliance, cross sectional area, and EGJ pressures (IRP and resting pressures) measured using HRM though there was no assessment of outcomes to determine, which measurement was more clinically relevant. In addition, in that cohort, 8/10 of the fundoplication patients had evidence of fundoplication unwrapping making a direct comparison with our study more difficult as very few patients in the present study had evidence of fundoplication unwrapping (1). Furthermore, in pediatrics, clinicians are often more concerned about EGJ obstruction rather than unwrapping; EGJ obstruction related to fundoplication is such a significant problem that more than 25% of all pediatric patients with fundoplication ultimately need their fundoplication dilated (11).

Our study shows that the distensibility of patients after fundoplication was low in 33% of patients and, in some cases, similar to the distensibility of achalasia patients. This reduced distensibility has been reported in some adult studies. In a compilation review of all adult FLIP studies, fundoplication patients from 2 studies had an EGJ distensibility ranging from 0.97 to 1.6 mm2/mmHg, which is a reduction of distensibility of 50 to 500% over GERD patients without fundoplication (3) Rinsma et al (12) performed HRM and FLIP measurements before and after fundoplication in 15 adult patients; whereas the authors found a reduction in distensibility and an increase in resting EGJ pressures after fundoplication, the correlation between distensibility, integrated relaxation pressures, bolus flow, and response to therapies were not addressed. A second study by Kwiatek et al (1) was performed intraoperatively on 17 adults at the time of the fundoplication so it is not clear how those results would relate to postoperative pediatric patients; however, the authors did not find a significant correlation between IRP and distensibility in their 13 out of 17 patients that had both FLIP and HRM. One challenge in children is that it is difficult to perform the same protocol in all ages of children for the fear of esophageal damage; clinicians’ initial instinct may be to underinflate the FLIP balloon to avoid complications. In fact, in our study, we found a significant difference in distensibility depending on the balloon inflation size per kg. Our study provides important guidance to pediatric gastroenterologists who may be able to plan the ideal inflation per kilogram based on the results of this study.

Another important finding in this study is that distensibility measured by FLIP is complementary to HRIM. In a single adult study, that reports both IRP and distensibility in 32 fundoplication patients and 25 achalasia patients, 38% of fundoplication patients had evidence of EGJ outflow tract obstruction based on a median IRP value of 14 (IQR 9–21) and a median distensibility of 3.5 (IQR 1.6–5.9) mm2/mmHg (4). In our cohort of patients who had a EGJ intervention, the median IRP was 13.9 ± 6.1 mmHg and the mean distensibility was 2.4 ± 1 mm2/mmHg.

There is a precedent in the literature to intervene endoscopically with low distensibilities. We found that 82% of fundoplication patients with low distensibility that underwent an EGJ intervention improved symptomatically. Although there are no equivalent adult studies, the value of a low distensibility to predict response to interventions has been previously shown in symptomatic patients with treated achalasia with FLIP better predicting symptomatic response and esophageal emptying compared with HRIM (13). As performing testing, such as FLIP and HRIM in healthy children is not ethically feasible, the normal pediatric values for distensibility and IRP are not known, so knowing values for distensibility and IRP that merit intervention is also unknown. We chose the value of 2.8 mm2/mmHg based on adult achalasia studies suggesting obstruction below this level but we recognize that fundoplication physiology may be more complex and variable and merits additional study.

There is a single pediatric study looking at the safety of measuring EGJ distensibility in 18 patients presenting with dysphagia in whom esophageal dilation was being considered for conditions, such as esophageal strictures or achalasia (14). In that study, however, none of the patients had fundoplications and the median EGJ distensibility was 3.1 to 3.5 mm2/mmHg using 20 and 30 mL inflations suggesting that the EGJ function was not significantly impaired in that cohort. Although the authors conclude that the FLIP technology is safe to perform in pediatrics, their results are not generalizable to our fundoplication population and neither this pediatric study, nor any adult study links the FLIP findings to outcomes.

In our study, FLIP and HRIM provide complementary information about EGJ physiology. As FLIP can be performed at the time of the index endoscopy, a normal FLIP would be therefore be reassuring that an HRIM may not be needed. HRIM is a very difficult test to perform in young children who are crying for much of the study or are unable to tolerate the saline swallows. On the basis of these results, FLIP could be used in lieu of HRIM in the majority of patients, thus reducing the number of pediatric procedures and potentially cost.

There are several limitations to this study. First, this is a small cohort of patients but the number of fundoplication patients in our study is similar to other adult studies. Furthermore, this is the first pediatric study using FLIP compared with HRIM so we think this study is an important addition to the literature, particularly as we provide insight into appropriate balloon inflation sizes in small children. On the basis of our results, we did include inflation size adjusted by weight to try to find a measure that could be applied to all pediatric patients in the future. Another possible limitation is the differences in IRPs between catheters. MMS catheters may result in a higher IRP, which may have given an appearance of a more obstructed esophagus than if a Medtronic catheter was used. We did not find a difference in the mean IRPs between catheters. In fact, we found that IRP regardless of the catheter used did not have a significant impact on clinical decision compared with FLIP though we do feel that prospective studies are needed to reduce bias. Another limitation is the lack of true controls, a known limitation of pediatric research. Finally, it is possible the clinical interventions were guided by 1 technology over another, or by symptom severity or other biases.

In conclusion, we show FLIP may provide additional insight into EGJ physiology in symptomatic fundoplication patients and complements HRIM.

Acknowledgments

This work was supported by R01 DK097112, the Boston Children's Hospital Translational Research Program Senior Investigator Award and the Birtwistle Family Fund.

REFERENCES

1. Kwiatek MA, Kahrilas K, Soper NJ, et al. Esophagogastric junction distensibility after fundoplication assessed with a novel functional luminal imaging probe. J Gastrointest Surg 2010; 14:268–276.
2. Hirano I, Pandolfino JE, Boeckxstaens GE. Functional lumen imaging probe for the management of esophageal disorders: expert review from the Clinical Practice Updates Committee of the AGA Institute. Clin Gastroenterol Hepatol 2017; 15:325–334.
3. Chen JW, Rubenstein JH. Esophagogastric junction distensibility assessed using the functional lumen imaging probe. World J Gastroenterol 2017; 23:1289–1297.
4. Carlson DA, Kahrilas PJ, Ritter K, et al. Mechanisms of repetitive retrograde contractions in response to sustained esophageal distension: a study evaluating patients with postfundoplication dysphagia. Am J Physiol Gastrointest Liver Physiol 2018; 314:G334–G340.
5. Pandolfino JE, de Ruigh A, Nicodeme F, et al. Distensibility of the esophagogastric junction assessed with the functional lumen imaging probe (FLIP) in achalasia patients. Neurogastroenterol Motil 2013; 25:496–501.
6. Kahrilas PJ, Bredenoord AJ, Fox M, et al. International High Resolution Manometry Working Group. The Chicago Classification of esophageal motility disorders, v3.0. Neurogastroenterol Motil 2015; 27:160–174.
7. Rosen R, Rodriguez L, Nurko S. Pediatric rumination subtypes: a study using high-resolution esophageal manometry with impedance. Neurogastroenterol Motil 2017; 29doi: 10.1111/nmo.12998.
8. Singendonk MM, Kritas S, Cock C, et al. Applying the Chicago Classification criteria of esophageal motility to a pediatric cohort: effects of patient age and size. Neurogastroenterol Motil 2014; 26:1333–1341.
9. Lin Z, Kahrilas PJ, Roman S, et al. Refining the criterion for an abnormal integrated relaxation pressure in esophageal pressure topography based on the pattern of esophageal contractility using a classification and regression tree model. Neurogastroenterol Motil 2012; 24:e356–e363.
10. Ponds FA, Bredenoord AJ, Kessing BF, et al. Esophagogastric junction distensibility identifies achalasia subgroup with manometrically normal esophagogastric junction relaxation. Neurogastroenterol Motil 2017; 29doi: 10.1111/nmo.12908.
11. Schneider A, Gottrand F, Sfeir R, et al. Postoperative lower esophageal dilation in children following the performance of Nissen fundoplication. Eur J Pediatr Surg 2012; 22:399–403.
12. Rinsma NF, Smeets FG, Bruls DW, et al. Effect of transoral incisionless fundoplication on reflux mechanisms. Surg Endosc 2014; 28:941–949.
13. Teitelbaum EN, Boris L, Arafat FO, et al. Comparison of esophagogastric junction distensibility changes during POEM and Heller myotomy using intraoperative FLIP. Surg Endosc 2013; 27:4547–4555.
14. Ng K, Mogul D, Hollier J, et al. Utility of functional lumen imaging probe in esophageal measurements and dilations: a single pediatric center experience. Surg Endosc 2019; [Epub ahead of print].
Keywords:

distensibility; esophagogastric junction obstruction; functional luminal imaging probe; fundoplication; gastroesophageal reflux disease; high-resolution manometry

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