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. Author manuscript; available in PMC: 2014 Feb 1.
Published in final edited form as: Clin Gastroenterol Hepatol. 2012 Oct 16;11(2):131–137. doi: 10.1016/j.cgh.2012.10.015

A Comparison of Symptom Severity and Bolus Retention to Chicago Classification Esophageal Pressure Topography Metrics in Patients with Achalasia

Frédéric Nicodème 1,2, Annemijn de Ruigh 1,3, Yinglian Xiao 1,4, Shankar Rajeswaran 5, Ezra N Teitelbaum 6,7, Eric S Hungness 6, Peter J Kahrilas 1, John E Pandolfino 1
PMCID: PMC3552153  NIHMSID: NIHMS429637  PMID: 23078890

Abstract

Background & Aims

We compared findings from timed barium esophagrams (TBEs) and esophageal pressure topography (EPT) studies among achalasia subtypes and in relation to symptom severity.

Method

We analyzed data from 50 patients with achalasia (31 male, 20–79 years old) who underwent high-resolution manometry (HRM), had TBE following a 200ml barium swallow, and completed questionnaires that determine Eckardt Scores (ES). Twenty-five were not treated and 25 were treated (11 by pneumatic dilation, 14 by myotomy). Non-parametric testing was used to assess differences among groups of treated patients (10 had type-1 achalasia and 15 had type-2 achalasia), and the Pearson correlation was used to assess their relationship.

Results

There were no significant differences in TBE measurements between patient groups. Of the 25 patients who received treatment, 10 had a manometric pattern consistent with persistent achalasia after treatment (6 with type 1 and 4 with type 2 achalasia), whereas 15 appeared to have resolved the achalasia pattern (peristalsis was absent in 8 and weak in 7). The height of the barium column at 5 minutes and ES were significantly reduced in patients that had resolved their achalasia pattern, based on HRM. The integrated relaxation pressure (IRP) and the TBE column height correlated at 5 minutes (r=0.422; p<0.05).

Discussion

Patients that resolve their achalasia pattern, based on HRM, demonstrated improved emptying based on TBE measurements and improved symptom scores. There was no significant difference between patients with type-1 or 2 achalasia in TBEs. These findings indicate that normalization of the IRP on HRM is a clinically relevant objective of treatment for achalasia.

Keywords: Achalasia, manometry, esophagram, symptom

INTRODUCTION

Achalasia is diagnosed by demonstrating dysfunction of lower esophageal sphincter (LES) relaxation and aperistalsis in the absence of obstructive pathology. The major modalities utilized to establish the diagnosis and manage the disease are endoscopy, timed barium esophagram (TBE) and esophageal manometry. A TBE quantifies delayed esophageal emptying as a surrogate marker of esophagogastric junction (EGJ) dysfunction, may identify the characteristic ‘bird beak’ configuration at the LES, and details the degree of dilatation or sigmoid appearance. However, both TBE and endoscopy may be normal in achalasia patients1,2 as they do not detect the early physiological dysfunction of the disease. Hence, manometry has become the ‘gold standard’ for diagnosing achalasia.

High-resolution manometry (HRM) with esophageal pressure topography (EPT) has improved the accuracy of manometry in detecting achalasia and defined clinically relevant subtypes prior to treatment2–6. The achalasia subtypes are differentiated based on the patterns of esophageal pressurization and contraction during the 10-swallow protocol. However, no data exist to substantiate that HRM characteristics correlate with symptom severity or treatment efficacy. Hence, we hypothesized that the EPT features used to distinguish type 1 from type 2 achalasia would translate into differences on TBE before therapy and that improvement in EPT metrics of EGJ function after treatment would be associated with improved symptoms and reduced bolus retention.

The aim of this study was to assess the relationship between contractile and pressurization patterns defined on EPT, clinical endpoints of bolus retention on TBE, and symptom severity in type 1 and 2 achalasia. Additionally, we sought to compare EPT and TBE metrics as measures of treatment efficacy.

MATERIALS AND METHODS

Subjects

Fifty non-spastic achalasia patients (31 Males; 20–79 yo) were prospectively recruited into two separate cohorts. The first cohort of 25 patients was enrolled from the clinic at the Northwestern Esophageal Center based on a new diagnosis of type 1 or 2 achalasia. All 25 patients underwent endoscopy, HRM, TBE, and symptom assessment before treatment. A second cohort of 25 treated patients were enrolled based on having had pre-treatment type 1 or 2 achalasia and now undergoing our post-treatment study protocol including HRM, TBE, endoscopy, and symptom assessment. Only types 1 and 2 were included in the study because the spastic contractions in type 3 achalasia have unique features on TBE and EPT that are independent of bolus retention and sphincter function. HRM and TBE studies were done within 1 month of each other. All subjects gave written informed consent. The Northwestern University Institutional Review Board approved the study protocol.

Symptom assessment

For all 50 patients, dysphagia, regurgitation, retrosternal pain and weight loss were assessed to calculate the Eckardt Score (ES)7–11, each graded from 0 to 3. Patients were classified as having a good outcome if ES was <3 or a poor outcome if ES ≥3.

High-resolution manometry

Manometric studies were conducted in the supine position after a six-hour fast. The HRM catheter was a 4.2mm outer diameter solid-state assembly with 36 circumferential sensors spaced 1cm apart (Given Imaging, Duluth GA, USA). The HRM assembly was calibrated at 0 and 300mmHg and placed transnasally. The HRM assembly was positioned during endoscopy in instances of challenging anatomy, strong patient preference, or prior experience suggesting that that would be necessary. In those instances, the manometry study was performed at least 2 hours after endoscopy. The manometric protocol included a 2-minute baseline recording and ten 5-ml swallows.

Manometry studies were analyzed using ManoView analysis software (Given Imaging, Duluth GA, USA). Key EPT metrics analyzed were: integrated relaxation pressure (IRP)12,13, peristaltic integrity using the 20mmHg isobaric contour, distal contractile integral, contractile front velocity, and the distal latency1,14. The key metric in achalasia is the IRP, which quantify EGJ relaxation both in completeness and persistence. The upper limit of normal of the mean IRP for this protocol and instrumentation is <15mmHg3. Additional measures of EGJ function analyzed were the mean resting EGJ pressure at end-expiration during the 2-minute baseline recording and mean nadir EGJ relaxation pressure measured using the isobaric contour tool on ManoView software. 7,9–11.

Pressure patterns within the esophagus were characterized as in Figure 1.12. Peristaltic integrity was scored as intact (no break >2cm in the 20mmHg isobaric contour), weak (breaks >2cm in the 20mmHg isobaric contour), or failed (<3cm integrity of the 20mmHg isobaric contour distal to the transition zone)14.

Figure 1.

Figure 1

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The four potential HRM patterns after treatment of type 1 or 2 achalasia. Panels A and B represent persistent achalasia patterns. Panels C and D represent resolved achalasia patterns: absent peristalsis (Panel C) or weak peristalsis (Panel D).

The criteria used for defining type 1 achalasia in untreated patients were an IRP ≥15mmHg and 100% failed peristalsis. Pre-treatment type 2 achalasia was defined by an IRP ≥15mmHg and panesophageal pressurization in ≥20% of test swallows. The presence of premature contractions with ≥20% of test swallows or swallows exhibiting preserved peristalsis excluded the diagnosis of type 1 or 2 achalasia as these would be categorized as type 3 achalasia and EGJ outflow obstruction, respectively.

With post-treatment patients, the same definitions were utilized with the caveat that patients were no longer categorized as having an achalasia subtype if the post-treatment IRP was <15mmHg. Hence, patients were categorized as persistent achalasia (type 1 or 2) or a resolved achalasia pattern along with a description of the current manometric profile using the same Chicago Classification definitions as pre-treatment. We emphasize that a resolved achalasia pattern does not equate to resolution of the achalasia disease process.

Timed barium esophagram

TBEs were performed in the upright position to obtain frontal spot films of the esophagus at baseline, 1, 2, and 5 minutes after ingestion of 200ml (sometimes limited by patient tolerance) of low-density (45% weight to volume) barium sulphate. The height of the barium column was measured vertically from the EGJ using a lead scale placed directly on patient. The maximal esophageal diameter was measured along the esophageal body perpendicular to the axial plane of the esophagus.

Statistical analysis

Data from each patient cohort were analyzed independently. Continuous variables were expressed as median [25th–75th percentile]. We used the Mann-Whitney test to compare 2 samples, and the Kruskal-Wallis test to compare more than 2 samples using a significance level of p <0.05. Correlations were calculated using Pearson correlation coefficients.

RESULTS

The untreated cohort consisted of 17 males and 8 females; 31–67 years old. The treated cohort had 14 males and 11 females; 20–79 years old. Seven HRM studies (14%) were done after using endoscopy to position the HRM assembly. The untreated group consisted of 10 type 1 and 15 type 2 whereas the pre-treatment distribution of the treated group was of 15 type 1 and 10 type 2 achalasia patients. The treatments rendered were pneumatic dilation (n=11), laparoscopic Heller myotomy (LHM) (n=9), and per-oral endoscopic myotomy (POEM) (n=5).

Untreated patients

Type 2 untreated patients had a significantly greater IRP (24, IQR 18–33mmHg vs. mean 16, IQR 12–21mmHg) and nadir-relaxation pressure (20, IQR 14–29mmHg vs. mean 12, IQR 9–18mmHg) compared to the type 1 patients. Resting EGJ pressure (type 1: 15, IQR 12–21mmHg; type 2: 15, IQR 18–33mmHg), barium column height (type 1: 8.9cm, IQR 7–14cm; type 2: 7.0, IQR 6.0–11.5cm), and barium column width (type 1: 2.9, IQR 2.2–4cm; type 2: 3.4, IQR 3.0–4.1cm) were similar between achalasia subtypes (Figure 2). There was also no difference in ES for the type 1 (mean 5, IQR 5–6) and type 2 (mean 7.5, IQR 6.8–8.3) patients. No significant correlations were found between TBE column height at 5 minutes and IRP (r=−0.21, p=0.30), resting EGJ pressure (r=−0.04, p=0.85), nadir-EGJ relaxation pressure (r=−0.16, p=0.45), or ES (r=0.10, p=0.80). Similarly, there was no correlation between ES and IRP (r= 0.59, p=0.10), resting EGJ pressure (r=0.17, p=0.67), and nadir-EGJ relaxation pressure (r=0.63, p=0.07).

Figure 2.

Figure 2

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Examples of TBE and HRM studies for untreated patients. The TBE column height and width do not differentiate type 1 and type 2 achalasia.

Relationship between EPT findings, TBE findings, and treatment outcome

Ten post-treatment patients had EPT findings of persistent achalasia pattern (six type 1, four type 2) while fifteen had resolution of the achalasia pattern and converted to either absent peristalsis (n=8) or weak peristalsis (n=7). Table 1 compares HRM, TBE, and ES data of patients with persistent vs. resolved achalasia pattern. The IRP, resting EGJ pressure and nadir-EGJ were all significantly correlated with post-treatment ES: IRP r= 0.51, p=0.01; resting EGJ pressure r=0.43, p=0.04; nadir-EGJ relaxation pressure r= 0.44, p=0.03. Analyzing the EPT metrics dichotomously as normal or abnormal based on the predefined cutoff values showed a significant difference in both TBE-defined and ES-defined outcome for the IRP cutoff of 15mmHg, but not for the EGJ resting pressure or for the nadir-EGJ relaxation pressure (10mmHg) (Figure 3).

Table 1.

Characteristics of treated patients, median (IQR)

Persistent Achalasia Pattern Resolved Achalasia Pattern P value
HRM pattern 6 Type 1, 4 Type 2 8 absent, 7 weak peristalsis
Treatment PD=5, POEM=2, LHM=3 PD=6, POEM=3, LHM=6
IRP (mmHg) 19 (17–21) 8 (7–12) P <0.05
Resting EGJ pressure (mmHg) 15 (9–20) 7 (5–11) P <0.05
Nadir-EGJ relaxation pressure (mmHg) 14 (11–17) 7 (5–11) P <0.05
TBE 5 min (cm) 8 (7–10) 2 (0–5) P <0.05
TBE width (cm) 2.9 (1.3–3.3) 2.1 (1.2–3.5) NS
ES 4 (2–5) 1.5 (0–2) P <0.05
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EGJ- esophagogastric junction, IRP- integrated relaxation pressure, TBE- timed barium esophagram

Figure 3.

Figure 3

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TBE column height at 5 minutes and ES in patient groups defined by normal or abnormal EGJ metrics: Panel A, IRP; Panel B, resting EGJ pressure; Panel C, nadir-EGJ relaxation pressure. Note that only the IRP (<15mmHg or ≥15mmHg) segregates the patients into two significantly different groups (p <0.05).

TBE column height at 5 minutes (but not width), IRP and ES were significantly lower in patients with resolved achalasia pattern patterns on HRM than in patients with a persistent achalasia pattern (Figure 4). The subgroup of 7 patients with weak peristalsis appeared to have the best outcome: the median TBE column height at 5 minutes was significantly lower than the three other groups (p <0.05), and ES showed a trend toward a lower value compared to the other 3 groups (p=0.07).

Figure 4.

Figure 4

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Comparison of IRP (mmHg), TBE column height at 5 minutes (cm) and ES (median) among patients subdivided by post-treatment EPT pattern (types 1 and 2 achalasia, absent peristalsis, and weak peristalsis). The values of the 3 variables were lower in patients with a resolved achalasia pattern (p <0.05) suggesting this was indicative of consistently better outcome. The group that evolved to weak peristalsis appeared to have the best outcome with a significantly lower barium column height at 5 minutes (p <0.05) and a trend toward a lower ES compared to the other 3 groups.

There were no significant correlations between the TBE column height at 5 min and resting EGJ pressure (r=0.18, p=0.37) or nadir EGJ relaxation pressure in the post-treatment patients (r=0.27, p=0.20). Only the IRP showed a weak correlation (r=0.42, p= 0.05). The correlation between TBE column height at 5 min and ES after treatment was also not significant (r=0.31, p=0.24). However, the median TBE column height at 5 minutes for patients with an ES of ≥3 (6.9cm, IQR 6.7–8.2cm) was significantly greater than that for patients with an ES <3 (2.5cm, IQR 0–6.85cm). Assessing the best cutoff for TBE column height at 5 minutes for predicting a good response to the treatment suggested that a 5cm value was the optimal discriminator; 75% of patients with a TBE column height <5cm had an ES <3, while 54% of patients with a TBE column height >5cm had an ES ≥3. Using a 5cm cutoff to dichotomously define the TBE outcome as good or poor, the ES was significantly better in those with a good TBE outcome (TBE >5cm, median ES =3 (IQR 2–5); TBE <5cm, median ES =1.5 (IQR 0–2.25)). Similarly, the 5cm cutoff showed a trend to correlating with outcome gauged by the post-treatment IRP (TBE >5cm, median IRP =17.5mmHg (IQR 10–21); TBE <5cm, median IRP =8mmHg (IQR 7–13), p=0.06)). There was no relationship between maximal esophageal diameter on TBE and ES (r=−0.03, p=0.89)

Concordance between TBE and EPT in predicting symptom outcome

Plotting the TBE column height vs IRP revealed some discordance between the two techniques and symptom outcome (Figure 5). Although an abnormal IRP was never associated with complete emptying, there were multiple instances where a normal IRP was associated with bolus retention. However, most of these patients were asymptomatic and had a greater degree of esophageal dilatation. There were 3 patients with an IRP <15mmHg and a borderline abnormal ES of 3; one with no bolus retention, and 2 with minimal and moderate TBE bolus retention at 5 minutes (column heights of 1.5 and 5.5cm), suggesting that their symptoms were moderate. One subject had an IRP <15mmHg and continued to have evidence of severe bolus retention with minimal symptoms. This subject had severe dilatation on the TBE explaining the bolus retention. Concordance of abnormalities on TBE and IRP was associated with a poor ES in 5 of the 7 such patients. The two patients with ES <3 despite abnormal emptying and an IRP >15mmHg were both type 2 achalasia patients that had a major reduction in IRP after treatment (54 to 17mmHg and 33 to 22mmHg).

Figure 5.

Figure 5

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Relationship between IRP (mmHg) and TBE column height at 5 minutes (cm) defined by post-treatment ES and HRM pattern. Resolution of the HRM achalasia pattern was associated with a greater likelihood to have an ES <3. There were no instances where the IRP was abnormal and complete emptying occurred. Patients also tended to have better outcomes when both the IRP and barium column height were less that cutoff values (IRP <15mmHg, TBE column height <5cm), but there were two patients that continued to have symptoms despite minimal bolus retention and low IRP values.

DISCUSSION

This investigation represents the first study to assess whether HRM-EPT metrics correlate with symptom severity and bolus retention on TBE in achalasia patients before or after treatment. Our findings suggest that resolution of the achalasia pattern on EPT after treatment was associated with an improvement in symptoms and reduced bolus retention. Although the IRP was not strongly linearly correlated with symptom severity, when analyzed dichotomously patients with an IRP ≥15mmHg had worse symptom scores and greater bolus retention on TBE compared to those with normal IRP values. In contrast, no EPT pattern, EPT metric or TBE variable predicted symptom severity in untreated achalasia patients. Furthermore, barium height on TBE did not distinguish achalasia EPT subtypes. These findings suggest that in addition to its proven utility in detecting pre-treatment achalasia, EPT also has utility in the management of post-treatment achalasia that can complement TBE.

TBE is useful to diagnose achalasia and to assess for dilatation and sigmoid configuration, features suggesting worse prognosis. Additionally, bolus retention on TBE is a useful metric in assessing treatment outcome in that it can substantiate the necessity for further treatment2,2,4–6. On the other hand, although most clinical guidelines advise that the diagnosis of achalasia requires manometric evaluation, some suggest that manometry is not required in post-treatment management8,15. Although an EGJ pressure after treatment of <10mmHg has been identified as indicative of good outcome, there are conflicting reports regarding the utility of this measurement in the evaluation of post-treatment success13,16,17. We hypothesized that the greater detail and the improved accuracy of measurement provided by HRM with EPT analysis could improve the value of manometry in post-treatment management. Our findings suggest that the resolution of the achalasia pattern on EPT was associated with better symptom scores and less bolus retention. Of the 15 post-treatment patients with a resolution of the achalasia pattern, 73% had bolus retention of ≤5cm at 5 minutes and 79% had an ES <3 indicative of a good outcome. Additionally, it appeared that the contractile pattern in the patients with a resolved achalasia pattern may have some significance as those patients exhibiting weak peristalsis after treatment had no bolus retention and a better ES compared to those with absent peristalsis. However, these numbers were small and this phenomenon will require a larger sample size before definitive conclusions can be made.

Although resolution of the achalasia pattern on EPT was helpful in substantiating a good outcome, IRP by itself exhibited only a weak correlation with ES and the TBE barium column height at 5 minutes. However, the relationship between these measures and symptom outcome is unlikely to be linear with a strong Pearson correlation. Our findings suggest a threshold value of IRP (15mmHg) was predictive of symptom improvement and that once a patient achieved that threshold, further reduction in the IRP may not provide further benefit. This is evident in Figure 4 where it appears that the IRP threshold of <15mmHg was associated with better ES and less bolus retention on TBE.

The barium column height at 5 minutes on TBE was also not significantly correlated with ES, again highlighting that these tests probably function better with discrete target cutoff values as opposed to assessing correlation in a linear fashion. Our analysis suggests that a value of 5cm for the TBE column height at 5 minutes was a reasonable target outcome as the median barium height on TBE at 5 minutes in patients with an ES ≥3 was 6.9cm (IQR 6.7–8.2cm) and 5cm appeared to best discriminate positive and negative outcomes in this limited data set. Of note, a recent randomized controlled trial assessing pneumatic dilation versus myotomy proposed a column height of less than 10cm as the target column height for TBE utilizing the study to assess need for repeat pneumatic dilation. Clearly, further work is required in a larger series to define the optimal cutoff for barium column height to guide management.

Although the cutoff values for interpreting TBE and EPT studies suggested here and in previous publications appear reasonable as indicators of outcome success, the nature of achalasia as a dominant motor disorder in the early stages and a dominant anatomic disorder in the very late stages will invariably make certain measurements less useful in each situation. There are occasions that patients will continue to have a poor symptom outcome despite a resolution of the achalasia pattern or reduction of the IRP to less than 15mmHg because the disorder has evolved to where the anatomical deformity dominates the clinical picture. This was evident in Figure 5 where a single patient had a TBE with severe retention and dilatation despite having an IRP of 4mmHg and relatively mild symptoms. Conversely, there were patients who continued to have symptoms despite minimal to no bolus retention and a normal IRP suggesting that some patients may have a component of hypersensitivity to minimal transit abnormalities or a component of reflux driving the persistent symptoms.

In conclusion, our findings suggest that EPT is useful in the evaluation of achalasia after treatment and that normalizing the IRP was associated with a good symptom outcome. The best symptomatic outcome was seen in individuals who evolved to a weak peristalsis pattern. Additionally, TBE did not distinguish type 1 from type 2 achalasia and, the ability to identify these subtypes appears to be unique to EPT. However, TBE does complement EPT especially when the disease has progressed to an anatomic-dominant disorder. Future studies need to be performed in a large series of patients before and after therapy to confidently establish the relative merits of each evaluation in terms of predicting long-term outcome and cost-effectiveness.

Acknowledgments

This work was supported by R01 DK079902 (JEP) and R01 DK56033 (PJK) from the Public Health Service

Abbreviations

HRM

high-resolution manometry

EPT

esophageal pressure topography

TBE

timed barium esophagram

EGJ

esophagogastric junction

IRP

integrated relaxation pressure

ES

Eckardt Score

Footnotes

Disclosures: No relevant competing financial and other interests exist for Frédéric Nicodème, Annemijn de Ruigh, Yinglian Xiao, Shankar Rajeswaran, Ezra N. Teitelbaum, Eric S. Hungness, Peter J. Kahrilas and John E. Pandolfino.

Author contributions:

Frédéric Nicodème contributed to the conception and study design, study supervision, data collection, analysis and interpretation, statistical analysis, manuscript drafting, editing, critical revision and final approval.

Annemijn de Ruigh contributed to data analysis and interpretation, and manuscript final approval.

Yinglian Xiao contributed to analysis and interpretation, critical revision and final approval.

Shankar Rajeswaran contributed to data collection and analysis, and final approval.

Ezra N. Teitelbaum contributed to data collection and analysis, and final approval.

Eric S. Hungness contributed to the conception and study design, data interpretation, critical revision and final approval.

Peter J. Kahrilas contributed to the conception and study design, obtained funding, data interpretation, editing, critical revision and final approval.

John E. Pandolfino contributed to the conception and study design, obtained funding, data interpretation, manuscript editing, critical revision and final approval.

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