Achalasia is diagnosed by showing dysfunction of lower

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1 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2013;11: ALIMENTARY TRACT A Comparison of Symptom Severity and Bolus Retention With Chicago Classification Esophageal Pressure Topography Metrics in Patients With Achalasia FRÉDÉRIC NICODÈME,*, ANNEMIJN DE RUIGH,*, YINGLIAN XIAO,*, SHANKAR RAJESWARAN, EZRA N. TEITELBAUM, #, ** ERIC S. HUNGNESS, # PETER J. KAHRILAS,* and JOHN E. PANDOLFINO* *Department of Medicine, Department of Radiology, # Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Department of Thoracic Surgery, Centre Hospitalier de l Université de Montréal, Montréal, Québec, Canada; Department of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands; Department of Gastroenterology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; and **Department of Surgery, George Washington University, Washington, District of Columbia This article has an accompanying continuing medical education activity on page e15. Learning Objectives At the end of this activity, the successful learner will review the assessment and management of a patient with achalasia using high-resolution manometry and the Chicago classification. BACKGROUND & AIMS: We compared findings from timed barium esophagrams (TBEs) and esophageal pressure topography studies among achalasia subtypes and in relation to symptom severity. METHODS: We analyzed data from 50 patients with achalasia (31 men; age, y) who underwent high-resolution manometry (HRM), had TBE after a 200-mL barium swallow, and completed questionnaires that determined Eckardt Scores. Twenty-five patients were not treated, and 25 patients were treated (11 by pneumatic dilation, 14 by myotomy). Nonparametric 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 patients with type 1 and 4 patients with type 2 achalasia), whereas 15 appeared to have resolved the achalasia pattern (peristalsis was absent in 8 patients and weak in 7 patients). The height of the barium column at 5 minutes and Eckardt Scores were reduced significantly in patients who had resolved their achalasia pattern, based on HRM. The integrated relaxation pressure and the TBE column height correlated at 5 minutes (r 0.422; P.05). CONCLUSIONS: Patients who resolved their achalasia pattern, based on HRM, showed improved emptying based on TBE measurements and improved symptom scores. There was no significant difference between patients with type 1 or type 2 achalasia in TBEs. These findings indicate that normalization of the integrated relaxation pressure on HRM is a clinically relevant objective of treatment for achalasia. Keywords: Achalasia; Manometry; Esophagram; Symptom. Watch this article s video abstract and others at tiny.cc/bz9jv. Scan the quick response (QR) code to the left with your mobile device to watch this article s video abstract and others. Don t have a QR code reader? Get one by searching QR Scanner in your mobile device s app store. Achalasia is diagnosed by showing dysfunction of lower esophageal sphincter relaxation and aperistalsis in the absence of obstructive pathology. The major modalities used 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 lower esophageal sphincter, and details the degree of dilatation or sigmoid appearance. However, both TBE and endoscopy may be normal in achalasia patients 1,2 because 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 before treatment. 2 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 end points of bolus retention on TBE, and symptom severity in type 1 and type 2 achalasia. In addition, we sought to compare EPT and TBE metrics as measures of treatment efficacy. Abbreviations used in this paper: EGJ, esophagogastric junction; EPT, esophageal pressure topography; ES, Eckardt score; HRM, highresolution manometry; IRP, integrated relaxation pressure; TBE, timed barium esophagram by the AGA Institute /$

2 132 NICODÈME ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 11, No. 2 Materials and Methods Subjects Fifty nonspastic achalasia patients (31 men; age, y) prospectively were recruited into 2 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 type 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 pretreatment type 1 or type 2 achalasia and were 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 performed 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 less than 3 or a poor outcome if ES was 3 or greater. High-Resolution Manometry Manometric studies were conducted in the supine position after a 6-hour fast. The HRM catheter was a 4.2-mm outer-diameter solid-state assembly with 36 circumferential sensors spaced 1 cm apart (Given Imaging, Duluth, GA). The HRM assembly was calibrated at 0 and 300 mm Hg and placed transnasally. The HRM assembly was positioned during endoscopy in instances of challenging anatomy, strong patient preference, or prior experience suggesting 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). Key EPT metrics analyzed were integrated relaxation pressure (IRP), 12,13, nadir lower esophageal sphincter pressure, peristaltic integrity using the 20 mm Hg isobaric contour, distal contractile integral, contractile front velocity, and the distal latency. 1,14 The key metric in achalasia is the IRP, which quantifies EGJ relaxation both in completeness and persistence. The upper limit of normal of the mean IRP for this protocol and instrumentation is less than 15 mm Hg. 3 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 Peristaltic integrity was scored as intact (no break 2 cm in the 20 mm Hg isobaric contour), weak (breaks 2 cm in the 20 mm Hg isobaric contour), or failed ( 3 cm integrity of the 20 mm Hg isobaric contour distal to the transition zone). 14 The criteria used for defining type 1 achalasia in untreated patients were as follows: an IRP of 15 mm Hg or greater and 100% failed peristalsis. Pretreatment type 2 achalasia was defined as follows: an IRP of 15 mm Hg or greater and panesophageal pressurization in 20% or more of test swallows. The presence of premature contractions with 20% or more of test swallows or swallows showing preserved peristalsis excluded the diagnosis of type 1 or 2 achalasia because these would be categorized as type 3 achalasia and EGJ outflow obstruction, respectively. With post-treatment patients, the same definitions were used with the caveat that patients were no longer categorized as having an achalasia subtype if the post-treatment IRP was less than 15 mm Hg. Hence, patients were categorized as having 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 pretreatment. 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, and at 1, 2, and 5 minutes after ingestion of 200 ml (sometimes limited by patient tolerance) of low-density (45% weight to volume) barium sulfate. The height of the barium column was measured vertically from the EGJ using a lead scale placed directly on the 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 the 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 less than.05. Correlations were calculated using the Pearson correlation coefficient. Results The untreated cohort consisted of 17 men and 8 women, ages 31 to 67 years. The treated cohort had 14 men and 11 women, ages 20 to 79 years. Seven HRM studies (14%) were performed after using endoscopy to position the HRM assembly. The untreated group consisted of 10 type 1 and 15 type 2 achalasia patients, whereas the pretreatment distribution of the treated group was 15 type 1 and 10 type 2 achalasia patients. The treatments rendered were pneumatic dilation (n 11), laparoscopic Heller myotomy (n 9), and per-oral endoscopic myotomy (n 5). Untreated Patients Type 2 untreated patients had a significantly greater IRP (24; interquartile range [IQR], mm Hg vs mean, 16; IQR mm Hg) and nadir-relaxation pressure (20; IQR, mm Hg vs mean, 12; IQR, 9 18 mm Hg) compared with the type 1 patients. Resting EGJ pressure (type 1, 15; IQR, mm Hg; type 2, 15; IQR, mm Hg), barium column height (type 1, 8.9 cm; IQR, 7 14 cm; type 2, 7.0; IQR, cm), and barium column width (type 1, 2.9; IQR, cm; type 2, 3.4; IQR, cm) were similar between achalasia subtypes (Figure 2). There were also no differences in ES for the type 1

3 February 2013 ACHALASIA: HRM, ESOPHAGRAM, AND ECKARDT SCORE 133 Figure 1. The 4 potential HRM patterns after treatment of type 1 or type 2 achalasia. (A and B) Persistent achalasia patterns. (C and D) Resolved achalasia patterns: (C) absent peristalsis or (D) weak peristalsis. (mean, 5; IQR, 5 6) and type 2 (mean, 7.5; IQR, ) patients. No significant correlations were found between TBE column height at 5 minutes and IRP (r 0.21, P.30), resting EGJ pressure (r 0.04, P.85), nadir EGJ relaxation pressure (r 0.16, P.45), or ES (r 0.10, P.80). Similarly, there was no correlation between ES and IRP (r 0.59, P.10), resting EGJ pressure (r 0.17, P.67), and nadir EGJ relaxation pressure (r 0.63, P.07). Relationship Between Esophageal Pressure Topography Findings, Timed Barium Esophagram Findings, and Treatment Outcome Ten post-treatment patients had EPT findings of persistent achalasia pattern (6 type 1 patients and 4 type 2 patients), whereas 15 patients 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 all were correlated significantly with post-treatment ES, as follows: IRP, r 0.51, P.01; resting EGJ pressure, r 0.43, P.04; and nadir EGJ relaxation pressure, r 0.44, P.03. Analyzing the EPT metrics dichotomously as normal or abnormal based on the predefined cut-off values showed a significant difference in both TBE-defined and ES-defined outcome for the IRP cut-off value of 15 mm Hg, but not for the EGJ resting pressure or for the nadir EGJ relaxation pressure (10 mm Hg) (Figure 3). TBE column height at 5 minutes (but not width), IRP, and ES were significantly lower in patients with resolved achalasia 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 in the 3 other groups (P.05), and ES showed a trend toward a lower value compared with the other 3 groups (P.07). There were no significant correlations between the TBE column height at 5 minutes and resting EGJ pressure (r 0.18,

4 134 NICODÈME ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 11, No. 2 Figure 2. Examples of TBE and HRM studies for untreated patients. The TBE column height and width do not differentiate type 1 and type 2 achalasia. P.37) or nadir EGJ relaxation pressure in the post-treatment patients (r 0.27, P.20). Only the IRP showed a weak correlation (r 0.42, P.05). The correlation between TBE column height at 5 minutes and ES after treatment also was not significant (r 0.31, P.24). However, the median TBE column height at 5 minutes for patients with an ES of 3 or greater (6.9 cm; IQR, cm) was significantly greater than that for patients with an ES less than 3 (2.5 cm; IQR, cm). Assessing the best cut-off value for TBE column height at 5 minutes for predicting a good response to the treatment suggested that a 5-cm value was the optimal discriminator; 75% of patients with a TBE column height less than 5 cm had an ES less than 3, whereas 54% of patients with a TBE column height greater than 5 cm had an ES of 3 or greater. By using a 5-cm Table 1. Characteristics of Treated Patients, Median Persistent achalasia pattern Resolved achalasia pattern P value HRM pattern 6 type 1 patients, 4 type 2 patients 8 absent, 7 weak peristalsis Treatment PD, 5 patients; POEM, 2 patients; LHM, 3 patients PD, 6 patients; POEM, 3 patients; LHM, 6 patients IRP, mm Hg (IQR) 19 (17 21) 8 (7 12).05 Resting EGJ pressure, mm Hg (IQR) 15 (9 20) 7 (5 11).05 Nadir EGJ relaxation pressure, mm Hg (IQR) 14 (11 17) 7 (5 11).05 TBE 5 minutes, cm (IQR) 8 (7 10) 2 (0 5).05 TBE width, cm (IQR) 2.9 ( ) 2.1 ( ) NS ES 4 (2 5) 1.5 (0 2).05 LHM, laparoscopic Heller myotomy; PD, pneumatic dilation; POEM, per-oral endoscopic myotomy.

5 February 2013 ACHALASIA: HRM, ESOPHAGRAM, AND ECKARDT SCORE 135 Figure 3. TBE column height at 5 minutes and ES in patient groups defined by normal or abnormal EGJ metrics: (A) IRP, (B) resting EGJ pressure, and (C) nadir EGJ relaxation pressure. Note that only the IRP ( 15 or 15 mm Hg) segregates the patients into 2 significantly different groups (P.05). LES, lower esophageal sphincter pressure. cut-off value to dichotomously define the TBE outcome as good or poor, the ES was significantly better in those with a good TBE outcome (TBE, 5 cm; median ES, 3; IQR, 2 5; TBE, 5 cm; median ES, 1.5; IQR, ). Similarly, the 5-cm cut-off value showed a trend correlating with outcome gauged by the post-treatment IRP (TBE 5 cm: median IRP, 17.5 mm Hg; IQR, 10 21; TBE 5 cm: median IRP, 8 mm Hg; IQR, 7 13; P.06). There was no relationship between maximal esophageal diameter on TBE and ES (r 0.03, P.89). Concordance Between Timed Barium Esophagram and Esophageal Pressure Topography in Predicting Symptom Outcome Plotting the TBE column height vs IRP revealed some discordance between the 2 techniques and symptom outcome (Figure 5). Although an abnormal IRP was never associated with complete emptying, there were multiple instances in which a normal IRP was associated with bolus retention. However, most of these patients were asymptomatic and had a greater degree of Figure 4. Comparison of IRP (mm Hg), 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.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.05) and a trend toward a lower ES compared with the other 3 groups. Figure 5. Relationship between IRP (mm Hg) 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 less than 3. There were no instances in which 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 than the cut-off values (IRP 15 mm Hg, TBE column height 5 cm), but there were 2 patients who continued to have symptoms despite minimal bolus retention and low IRP values.

6 136 NICODÈME ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 11, No. 2 esophageal dilatation. There were 3 patients with an IRP less than 15 mm Hg and a borderline abnormal ES of 3; 1 patient with no bolus retention, and 2 patients with minimal and moderate TBE bolus retention at 5 minutes (column heights of 1.5 and 5.5 cm), suggesting that their symptoms were moderate. One subject had an IRP less than 15 mm Hg 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 2 patients with ES less than 3 despite abnormal emptying and an IRP greater than 15 mm Hg were both type 2 achalasia patients who had a major reduction in IRP after treatment (reduction: 54 to 17 mm Hg and 33 to 22 mm Hg). Discussion We performed this 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 of 15 mm Hg or greater had worse symptom scores and greater bolus retention on TBE compared with 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 pretreatment 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. In addition, bolus retention on TBE is a useful metric in assessing treatment outcome in that it can substantiate the necessity for further treatment. 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 management. 8,15 Although an EGJ pressure of less than 10 mm Hg after treatment has been identified as indicative of good outcome, there are conflicting reports regarding the utility of this measurement in the evaluation of post-treatment success. 13,16,17 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 5 cm or less at 5 minutes and 79% had an ES less than 3, which was indicative of a good outcome. In addition, it appeared that the contractile pattern in the patients with a resolved achalasia pattern may have some significance because those patients showing weak peristalsis after treatment had no bolus retention and a better ES compared with 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 showed 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 (15 mm Hg) 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, in which it appears that the IRP threshold of less than 15 mm Hg was associated with better ES and less bolus retention on TBE. The barium column height at 5 minutes on TBE also was not correlated significantly with ES, again highlighting that these tests probably function better with discrete target cut-off values as opposed to assessing correlation in a linear fashion. Our analysis suggests that a value of 5 cm for the TBE column height at 5 minutes was a reasonable target outcome because the median barium height on TBE at 5 minutes in patients with an ES of 3 or greater was 6.9 cm (IQR, cm), and 5 cm appeared to best discriminate positive and negative outcomes in this limited data set. Of note, a recent randomized controlled trial assessing pneumatic dilation vs myotomy proposed a column height of less than 10 cm as the target column height for TBE using the study to assess need for repeat pneumatic dilation. Clearly, further work is required in a larger series to define the optimal cut-off value for barium column height to guide management. Although the cut-off 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 invariably will 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 15 mm Hg because the disorder has evolved to where the anatomic deformity dominates the clinical picture. This was evident in Figure 5 in which a single patient had a TBE with severe retention and dilatation despite having an IRP of 4 mm Hg 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. In addition, 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.

7 February 2013 ACHALASIA: HRM, ESOPHAGRAM, AND ECKARDT SCORE 137 References 1. Pandolfino JE, Ghosh SK, Rice J, et al. Classifying esophageal motility by pressure topography characteristics: a study of 400 patients and 75 controls. Am J Gastroenterol 2008;103: Vaezi MF, Baker ME, Achkar E, et al. Timed barium oesophagram: better predictor of long term success after pneumatic dilation in achalasia than symptom assessment. Gut 2002;50: Ghosh SK, Pandolfino JE, Rice J, et al. Impaired deglutitive EGJ relaxation in clinical esophageal manometry: a quantitative analysis of 400 patients and 75 controls. Am J Physiol Gastrointest Liver Physiol 2007;293:G878 G Salvador R, Costantini M, Zaninotto G, et al. The preoperative manometric pattern predicts the outcome of surgical treatment for esophageal achalasia. J Gastrointest Surg 2010;14: Pratap N, Kalapala R, Darisetty S, et al. Achalasia cardia subtyping by high-resolution manometry predicts the therapeutic outcome of pneumatic balloon dilatation. J Neurogastroenterol Motil 2011;17: Pandolfino JE, Kwiatek MA, Nealis T, et al. Achalasia: a new clinically relevant classification by high-resolution manometry. Gastroenterology 2008;135: Pandolfino JE, Ghosh SK, Zhang Q, et al. Quantifying EGJ morphology and relaxation with high-resolution manometry: a study of 75 asymptomatic volunteers. Am J Physiol Gastrointest Liver Physiol 2006;290:G1033 G Eckardt VF, Aignherr C, Bernhard G. Predictors of outcome in patients with achalasia treated by pneumatic dilation. Gastroenterology 1992;103: Bulsiewicz WJ, Kahrilas PJ, Kwiatek MA, et al. Esophageal pressure topography criteria indicative of incomplete bolus clearance: a study using high-resolution impedance manometry. Am J Gastroenterol 2009;104: Pandolfino JE, Kim H, Ghosh SK, et al. High-resolution manometry of the EGJ: an analysis of crural diaphragm function in GERD. Am J Gastroenterol 2007;102: Ghosh SK, Pandolfino JE, Kwiatek MA, et al. Oesophageal peristaltic transition zone defects: real but few and far between. Neurogastroenterol Motil 2008;20: Bredenoord AJ, Fox M, Kahrilas PJ, et al. Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography. Neurogastroenterol Motil 2012; 24(Suppl 1): Ghosh SK, Pandolfino JE, Zhang Q, et al. Deglutitive upper esophageal sphincter relaxation: a study of 75 volunteer subjects using solid-state high-resolution manometry. Am J Physiol Gastrointest Liver Physiol 2006;291:G525 G Roman S, Lin Z, Kwiatek MA, et al. Weak peristalsis in esophageal pressure topography: classification and association with dysphagia. Am J Gastroenterol 2011;106: Nayar DS, Khandwala F, Achkar E, et al. Esophageal manometry: assessment of interpreter consistency. Clin Gastroenterol Hepatol 2005;3: Eckardt AJ, Eckardt VF. Treatment and surveillance strategies in achalasia: an update. Nat Rev Gastroenterol Hepatol 2011;8: Fox M, Hebbard G, Janiak P, et al. High-resolution manometry predicts the success of oesophageal bolus transport and identifies clinically important abnormalities not detected by conventional manometry. Neurogastroenterol Motil 2004;16: Reprint requests Address requests for reprints to: John Pandolfino, MD, Department of Medicine, Division of Gastroenterology, Feinberg School of Medicine, Northwestern University, 676 St Clair Street, Suite 1400, Chicago, Illinois j-pandolfino@northwestern.edu; fax: (312) Conflicts of interest The authors disclose no conflicts. Funding This work was supported by R01 DK (J.E.P.) and R01 DK56033 (P.J.K.) from the Public Health Service.