Address for Correspondence Peter J. Kahrilas MD, Department of Medicine, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, 676 N. St. Clair Street, 14th Floor, Chicago, IL 60611, USA. Tel: +312 695 4016; fax: +312 695 3999; e-mail: email@example.com
Background The assessment of the esophagogastric junction (EGJ) is the most challenging aspect of clinical esophageal manometry. Although conventional manometric systems can be optimized toward interrogating specific aspects of the EGJ, they are too limited in recording channels and/or fidelity for a comprehensive assessment. The technological advantages inherent in high resolution manometry (HRM) with esophageal pressure topography (EPT) analysis substantially change this equation providing a technology sufficiently robust to dynamically record the contractile activity within the EGJ with both good fidelity and good spatial resolution.
Purpose This review is an update on our understanding of the application of HRM and EPT to the analysis of EGJ function. With respect to sphincter relaxation, the integrated relaxation pressure (IRP) has proven to be a robust metric in differentiating intact from impaired EGJ relaxation. In the process, it revealed that impaired EGJ relaxation could occur not only in the setting of achalasia but also with other causes of EGJ outflow obstruction including hiatus hernia. The morphological description of the EGJ by EPT has also revealed not only a spectrum of abnormality ranging from an intact sphincter to overt herniation, but also the surprise finding of spontaneous conversion among sphincter configurations, emphasizing its dynamic nature. With respect to barrier function, preliminary data have refocused on the crural diaphragm as a key-differentiating feature between preserved and compromised function. Finally, although the accomplishments summarized above are substantial, much work remains to fully exploit the potential of EPT in the clinical characterization of the EGJ.
The esophagogastric junction (EGJ) is the focal point for considerable esophageal pathophysiology, be it in the domain of gastro-esophageal reflux disease (GERD) or esophageal motility disorders. Esophagogastric junction incompetence is the most fundamental determinant of GERD. Impairment of neural control over the EGJ is the feature by which achalasia was named from the Greek, ‘not loosening’ (khalasis). Consequently, the assessment of EGJ competence and relaxation is a central aim of clinical manometry testing. However, several inherent attributes of EGJ pressure complicate its manometric assessment: (i) intraluminal pressure recorded within this region can be influenced by crural diaphragm (CD) contraction1 (which varies substantially with the respiratory cycle), (ii) lower esophageal sphincter (LES) contraction, the spatial relationship between the CD and the LES (potentially ranging from completely superimposed to completely disassociated),2 and (iii) the radial orientation of the sensor within the lumen which characteristically exhibits substantial radial pressure asymmetry.3 Hence, it is not surprising that the goal of defining manometric metrics for a normal or dysfunctional EJG has proven elusive.
High resolution manometry (HRM) with esophageal pressure topography (EPT) has the potential to overcome some of the limitations of EGJ manometrics experienced with earlier technologies. The basic concept of HRM is that by vastly increasing the number of pressure recording sites and decreasing the spacing between them, one can monitor intraluminal pressure without spatial gaps between recording sites.4,5 This feature overcomes two major limitations of conventional manometric recording: (i) the need to compensate for axial motion of sphincter elements with the use of a ‘sleeve’ device in the assessment of EGJ relaxation and (ii) the need to suspend respiration during a ‘pull-through’ assessment of the axial pressure profile within the EGJ. With HRM, EGJ pressure is dynamically monitored during normal respiration with defined axial resolution (usually 1 cm) and without artifacts attributable to swallow-induced sphincter movement5 or to EGJ conformational changes that may spontaneously occur.6 However, even within the domain of EPT, there are still a number of variables regarding the methodology for assessing EGJ relaxation, morphology, and competence (barrier function). Progress in the understanding of the optimal methodology for assessing the EGJ among these functional domains has been considerable with the widespread adoption of HRM into clinical practice. This review is organized as an update of this progress in each of these three areas.
Abnormal swallow-induced LES relaxation is a key element in defining achalasia. As such, the assessment of LES relaxation is a major objective of clinical manometry studies. Several nuances of quantifying LES relaxation emerge in EPT.5,7 Firstly, it is too simplistic to think of EGJ relaxation pressure as reflective only of LES relaxation. At any one instant, the pressure measured within the region of the EGJ is the greatest of three potential contributors: LES pressure, CD contraction, and intrabolus pressure as the swallowed water traverses the EGJ.5 Secondly, the CD is superimposed on the LES and swallowing does not inhibit CD contraction, which continues through the period of deglutitive LES relaxation.8,9 Consequently, other than in instances of hiatal hernia with complete axial separation between the LES and CD, one is actually measuring EGJ relaxation, not LES relaxation. Thirdly, swallow-induced peristalsis with contraction of the longitudinal muscle results in an average of 2 cm proximal migration of the LES.10 In extreme instances, this sphincter movement can be 9 cm.11 It has long been recognized that a single manometric sensor positioned within the sphincter prior to swallowing will end up within the stomach during swallow-induced esophageal contraction creating the artifact of ‘pseudorelaxation’.7 For all of these reasons, ‘nadir LES pressure’ as applied in conventional manometry, is a poor measure of incomplete deglutitive EGJ relaxation. Recognition of these deficiencies led to the development of a new EPT metric; the Integrated Relaxation Pressure (IRP).7 The IRP is measured within the spatial domain necessary to capture the axial movement of the LES in the postswallow period and spans the time from deglutitive upper sphincter relaxation until cessation of the distal peristaltic contraction (or 10 s in the absence of peristalsis). Thus, the IRP is similar to measuring EGJ relaxation with a Dent sleeve with the added stipulation that the number being reported is the average value for the 4 s of maximal relaxation after the swallow (Fig. 1). Table 1 illustrates improvement in the detection of impaired EGJ relaxation when IRP is compared with the ‘nadir LES pressure’ in a series of achalasia patients. This is important because failing to detect impaired EGJ relaxation in these patients would result in giving them an alternative diagnosis, most commonly misclassifying them as ineffective esophageal motility or DES.12
Table 1. Comparison of EGJ relaxation measures in 62 achalasia patients. The nadir pressure in conventional terms was the lowest pressure recorded from the sensor centered in the EGJ at the onset of the swallow, whereas the nadir EPT pressure accounted for sphincter movement after the swallow, in essence a nadir sleeve pressure. Both exhibited very poor sensitivity for detecting achalasia because of the subset of achalasics with brief periods of EGJ relaxation to within the normal range. On the other hand, the IRP requires persistence of EGJ relaxation for 4 s, skipping periods of CD contraction if necessary. Normal values were determined from 75 control subjects. Adapted from 
EGJ relaxation metric
Achalasia sensitivity %
False positives %
False negatives %
Nadir pressure, conventional (≥7 mmHg)
Nadir EPT pressure (≥10 mmHg)
Integrated relaxation pressure (≥15 mmHg)
The data detailed in the preceding paragraph were obtained using the Sierra (now Given Imaging) solid-state high resolution manometry assembly. This device uses unique pressure transduction technology (TactArray™, Given Imaging, Los Angeles, CA, USA) that allows each of the 36 pressure sensing elements to detect pressure in each of 12 radially dispersed sectors. The sector pressures are then averaged, making each of the 36 sensors a circumferential pressure detector with the extended frequency response characteristic of solid-state manometric systems.12 Among available technologies, the Sierra approach of averaging the electrical signal from 12 radially dispersed independent pressure sensors is unique. Ultimately, signal averaging may not prove to be the optimal approach as a strong argument can be made for preferentially reporting the lowest sector pressure. However, the Sierra device is currently the only device for which normal values of IRP have been published and whose performance has been tested clinically in the detection of achalasia, a key clinical application.7 Consequently, practitioners are cautioned against assuming that the same normative values and the 15 mmHg IRP threshold for the detection of impaired EGJ relaxation necessarily apply to other devices, be they from Given Imaging or other manufacturers.
Although utilizing the IRP in the EPT analysis of EGJ relaxation goes a long way toward clarifying the diagnosis in many achalasia patients that would otherwise be classified as ‘non-specific’ or misclassified to a non-achalasia diagnosis, there remains a group of patients with impaired EGJ relaxation failing to meet criteria for achalasia due to some preserved peristalsis. A series of 1000 consecutive patients studied with EPT included 16 such individuals with what has been termed ‘EGJ Outflow Obstruction’ exhibiting not only an IRP greater than 15 mmHg but also preserved peristalsis and elevated intrabolus pressure above the EGJ during peristalsis.13 The finding of an elevated intrabolus pressure proximal to the sphincter is important because it validates the physiological significance of impaired EGJ relaxation. From a physiological perspective, elevated intrabolus pressure is the consequence of the impaired relaxation. Recent work suggests that when EGJ outflow obstruction occurs as a consequence of incomplete relaxation, it is accompanied by a relative increase in the ratio of peristaltic amplitude in S3 vs S2, whereas this is not the case with mechanical obstruction.14 Nonetheless, EGJ Outflow Obstruction encompasses a heterogeneous group of patients with some individuals having an incomplete phenotype of achalasia and others probably having an undetected mechanical cause of EGJ outflow obstruction such as hiatus hernia, esophageal stenosis, or eosinophilic esophagitis. Consequently, it is a patient group that merits further evaluation with mucosal biopsies and imaging studies to exclude inflammatory or malignant etiologies, be that with computerized tomography or endoscopic ultrasound. Only after these possibilities have been fully explored should it be accepted as atypical achalasia.
Among the 16 patients with idiopathic EGJ Outflow Obstruction described in the previous section, three were noted to have hiatus hernias. In one of these instances, it was the crural diaphragm rather than the LES that appeared to be the focus of resistance to bolus transit, suggesting this be the cause of dysphagia. A subsequent report specifically focused on EGJ relaxation characteristics of patients with sliding hiatus hernia and dysphagia by selectively restricting the IRP measurement boundaries to the LES and crural diaphragm individually.15 A subset of 10 patients was found exhibiting a relative obstruction at the crural diaphragm with elevated intrabolus pressure extending through the LES, supporting the concept that sliding hiatus hernia could be responsible for dysphagia. Consequently, patients presenting with elevated EGJ relaxation pressure in the context of a small hiatus hernia require careful analysis of the discrete elements of the EGJ before making a diagnosis of achalasia.
Another complexity of the IRP measurement is in how to deal with recordings from patients with large hiatal hernias. With large hiatal hernias, there is complete separation between the LES and CD and also the potential that the distal end of the recording assembly did not cross the CD to gain exposure to sub-diaphragmatic intragastric pressure. Among a series of 2000 EPT studies, this difficulty was encountered in 63/111 (57%) of patients with a large hiatal hernia (at least 5 cm on EGD examination).16 The consequence of this is that the IRP cannot be accurately calculated as the intra-hernia pressure can be significantly lower than the intra-abdominal pressure causing a falsely elevated IRP. This would have led to a false positive diagnosis of achalasia in 3 of the 63 cases alluded to in the series above if the problem related to the large hernia were not recognized. In the setting where manometric data is key to clinical decision-making, placing the catheter endoscopically can usually overcome the problem.
As alluded to above, it is not possible to measure the IRP if the manometric catheter fails to traverse the EGJ. This can occur not only in the setting of hiatus hernia as just discussed but also in achalasia. In a 2000 patient series, this problem was encountered in 28 achalasia patients.16 However, although not optimal, 94% of these studies were still judged diagnostic of achalasia based on the observed patterns of esophageal pressurization and associated endoscopic data.
The conventional manometric assessment of EGJ competence has focused on LES pressure and length characteristics. Reflecting the diverse manometric methodology applied to sphincter measurements, there is no widely accepted convention on how to make these measurements.17,18 As an indication of disease severity and prognosis, not surprisingly, measurements of LES pressure have not proven terribly useful in the diagnostic assessment of GERD. The adoption of EPT has the potential to improve upon the limitations and clinical utility of LES pressure and length measurements. For example, EGJ pressure morphology can be dynamically monitored in a consistent fashion with normal respiration and with minimal movement-related artifact. Not only peak EGJ pressure but also the relative positions and vigor of the LES and CD components are definable. Considerable further work is necessary, however, to establish standardized measurement techniques and clinical correlations.
The spectrum of EGJ pressure morphology in EPT during normal respiration was described in a series of 75 control subjects and 156 patients undergoing evaluation for GERD.19 Inspiratory EGJ pressure was defined as the maximal or peak pressure occurring during the normal respiratory cycle. Expiratory EGJ pressure was defined as the pressure at the midpoint between adjacent inspirations with all EGJ pressures referenced to intragastric pressure. The respiratory inversion point (RIP) was localized as the axial position along the lumen of the EGJ at which the inspiratory EGJ pressure became less than the expiratory EGJ pressure. Conceptually, this is the position at which the external EGJ environment switches from intra-abdominal to intra-mediastinal pressure. The inspiratory augmentation of EGJ pressure was the difference between basal inspiratory pressure and basal expiratory pressure. This could have a positive or negative value.
Using both isobaric contour plots and spatial pressure variation plots, the EGJ could be classified into three subtypes based on the axial relationship between the maximal EJG pressure peak and the CD pressure peak. When there was a double-peaked EGJ pressure profile on an isobaric contour or spatial pressure variation plot during inspiration, the proximal peak was taken to be the LES and the distal peak to be the CD. The LES-CD separation was the distance separating the peaks at inspiration. With EGJ Type I, there is no discernible LES-CD separation because the CD was superimposed on the LES (Fig. 2). With a Type I EGJ, the EGJ pressure band often appears to move up and down with the respiratory cycle, suggesting that the LES and CD are tethered to each other, presumably by the phrenoesophageal ligament. With a Type II EGJ, there is minimal, but discernible, LES-CD separation making for a double-peaked pressure profile on the spatial pressure variation plot. However, the nadir pressure between the LES and CD peaks is still greater than gastric pressure (Fig. 2). Type II EGJ is not associated with hiatus hernia, but represents an intermediate condition in which LES-CD separation was >1 cm and <2 cm. With a Type II EGJ, respiratory movement, the EGJ pressure band is less apparent than with Type I, presumably because of laxity of the phrenoesophageal ligament. With a Type III EGJ, there is more than 2 cm LES-CD separation at inspiration (Fig. 2). This is the HRM signature of hiatus hernia. Two subtypes were discernible, IIIa and IIIb, with the distinction being that the respiratory inversion point is distal to the LES with IIIa and proximal to the LES in IIIb. Thus, inspiratory ‘augmentation’ of EGJ peak pressure often has a negative value with type IIIa but, by definition, is positive with IIIb.
An important consequence of these observations with respect to EGJ pressure morphology is that the EGJ morphology is dynamic and varies with time and activity, especially eating. Prolonged HRM recordings in patients with endoscopically demonstrated hiatal hernias revealed them to exhibit both Type I and Type II EGJ morphology and to migrate between conformations within the same study.6,20 Consumption of a liquid meal was associated with conversion from a Type II profile to a Type I profile for the subsequent 60–90 min.20 Similarly, three hour postprandial recordings in 16 patients with small hiatal hernias on endoscopy found a Type I profile 57% of the time and a Type II profile for the remainder of the recording.6
EGJ Barrier Function
Impaired EGJ barrier function leading to excessive reflux of gastric juice into the distal esophagus is the root cause of GERD. Reflux occurs as discrete events that can ultimately be attributed to LES hypotension overcome by abdominal straining or transient LES relaxations (TLESRs). However, most patients with GERD have normal LES pressure at rest and a normal frequency of TLESRs. Presumably, what sets them apart from control subjects is physiological dysfunction of the EGJ when faced with everyday challenges manifest by liquid reflux. A recent study compared EPT attributes of the EGJ of 75 asymptomatic controls to 156 patients whose GERD status was characterized by endoscopy and pH monitoring in an attempt to ascertain the most relevant variables. All patients reported a similar severity of GERD symptoms, but were categorized as EGD+ if they had esophagitis on endoscopy and pH+ if they had excessive esophageal acid exposure or a positive reflux-symptom association on an ambulatory esophageal pH monitoring study. The EGJ was characterized by morphology (Type I, II, IIIa, IIIb), LES-CD axial separation, inspiratory pressure, expiratory pressure, and magnitude of inspiratory pressure augmentation. The respiratory effects on EGJ pressure morphology among subject groups are summarized in Table 2. Mean LES-CD separation was similar between control subjects and EGD−/pH− patients. In contrast, EGD+ patients and EGD−/pH+ patients had significantly greater LES-CD separation. Moreover, as evident in Table 2, there was a significant difference in the expiratory EGJ pressure between controls and GERD patients. Furthermore, EGD+ and EGD−/pH+ patients had a significantly lower inspiratory EGJ augmentation when compared with asymptomatic controls or EGD−/pH− patients.
Table 2. LES-CD separation and EGJ pressure profile amongst control subjects and symptomatic patients subgrouped by objective measures of GERD (EGD, pH monitoring). Data from Pandolfino et al. 
EGD (−)/pH (−)
EGD (−)/pH (+)
anova, *P < 0.05 vs controls, †P < 0.05 vs EGD (+).
LES-CD separation (cm)
Expiratory EGJ pressure (mmHg)
Inspiratory EGJ augmentation (mmHg)
Although Table 2 suggests that multiple EPT metrics differentiated the GERD from non-GERD patients, these measurements are, to some degree, interdependent. Thus, logistic regression analysis was performed to prioritize potential manometric measures as independent variables using GERD as a categorical dependent outcome. End-expiratory EGJ pressure, LES-CD separation, and inspiratory EGJ augmentation were all significantly associated with GERD when controlling for age and BMI. However, a model that examined all EGJ parameters simultaneously while controlling for age and BMI revealed that inspiratory augmentation, BMI and age were the only variables with a statistically significant independent association. The parameter estimate for inspiratory augmentation was −0.07 (SE 0.03, P = 0.001) while those for age and BMI were 0.08 (SE 0.04, P = 0.04) and 0.13 (SE 0.03, P < 0.001), respectively.
The logistic regression analysis described in the previous section suggests that the only manometric variable independently associated with GERD as the dependent outcome was the magnitude of inspiratory augmentation of EGJ pressure. As a group, EGJ type III subjects had significantly less inspiratory augmentation compared with EGJ types I or II. Only nine EGJ type I subjects had a zero or negative value of inspiratory augmentation and all of these had either a positive EGD or a positive pH study. Furthermore, 25 of 27 of the EGJ type III subjects with zero or a negative value of inspiratory augmentation had either a positive EGD or a positive pH study. ROC analysis of the sensitivity and specificity for inspiratory EGJ augmentation as a predictor of pH or endoscopy positive GERD revealed that the specificity was 95% or better if the inspiratory augmentation was less than or equal to 4 mmHg. However, the sensitivity at that threshold was only 34%. The optimal cut point value for inspiratory augmentation was 10 mmHg with a sensitivity of 57% and specificity of 79%. The inter-relatedness among inspiratory augmentation, EGJ morphology subtype and GERD status is illustrated in Fig. 3. The shaded area of the Figure indicates depicts the group with an inspiratory augmentation of less than 10 mmHg, 79% of whom were in the GERD positive population. It should be recognized, however, that both the nature of high resolution pressure averaging methodology and the lack of standardized EGJ measurement techniques may contribute to the fact that EGJ characteristics were not more strongly associated with GERD.
Anatomical EGJ variables were also shown to be important during postprandial HRM recordings of 16 GERD patients with small hernias.6 In all patients, both single and double pressure profiles were observed with the prevalence of the double-peak profile ranging between 11% and 91% of the total time in individual patients. Fluoroscopic images of the relationship between an endoclip on the squamocolumnar junction and the diaphragm confirmed that the double peak profile was indicative of a hernia configuration. Reflux episodes, detected by impedance pH monitoring, were significantly more frequent in the hernia state (23.1 ± 5.1 per hour) than in the reduced state (12.2 ± 2.4 per hour). Interestingly, the increased reflux episodes were almost uniformly due to non-TLESR mechanisms, especially swallow-induced reflux.
Postsurgical EGJ assessment
The goal of antireflux surgery is to restore an anatomic and functionally competent gastro-esophageal barrier. Surgical techniques aim to correct diaphragmatic crural defects, re-establish an intra-abdominal esophageal segment, and enhance the pressure and length of the neo-high pressure zone at the EGJ via the extrinsic effects of the fundic wrap. Recent studies suggest that high resolution manometry and EPT may prove to be a significant advance over conventional manometry in dissecting out the complex functional alterations in the normal and abnormal postsurgical EGJ.
High resolution manometry has been used to assess the effects of both partial (Belsey) and complete (Nissen) fundoplication on TLESR frequency and EGJ pressure profiles in 20 postoperative patients.21 The EGJ pressure profile was minimally affected by partial fundoplication whereas Nissen fundoplication significantly increased nadir EGJ pressures. Whether the technique and/or geometry of the fundoplication affects nadir EGJ pressures remains unknown. This same group of investigators further assessed pre- and post-fundoplication EGJ dynamics and bolus transport in 12 patients using concurrent HRM and fluoroscopy. EGJ lengths were significantly increased, opening diameter decreased (0.6–1.0 cm) and nadir EGJ relaxation pressures were significantly greater following fundoplication. A greater intrabolus pressure was also seen postfundoplication. Finally, EGJ transit time significantly correlated with dysphagia scores postfundoplication. The increase in resistance in flow as a consequence of altered EGJ dynamics postoperatively resulted in significantly prolonged transit times for both liquid and solid bolus swallows.22 These preliminary studies suggest that HRM holds significant promise in the clinical and manometric assessment of both asymptomatic and symptomatic patients post antireflux surgery.
Summary and Future Directions
Historically, the assessment of the EGJ has been the most challenging aspect of clinical esophageal manometry. In part, this is because a comprehensive clinical assessment entails evaluation of sphincter morphology, barrier function with respect to GERD and deglutitive relaxation that is of fundamental importance in the diagnosis of esophageal motor disorders. Although conventional manometric systems can be optimized toward achieving any one of these objectives, they were simply too limited in recording channels and/or fidelity to accomplish all. Furthermore, optimizing the system in one domain typically compromised it in the others. The technological advantages inherent in HRM with EPT analysis have substantially changed this equation and for the first time provided a technology sufficiently robust to dynamically record the contractile activity within the EGJ with both good fidelity and good spatial resolution. However, with this new technology came new challenges, one of which was revising the criteria of manometric analysis to fit the new technology.
Considerable progress has been made in applying EPT to EGJ analysis. With respect to sphincter relaxation, the IRP has proven to be a robust metric in differentiating intact from impaired EGJ relaxation. In the process, it has come to light that impaired EGJ relaxation can occur not only in the setting of achalasia but also with other causes of EGJ outflow obstruction including hiatus hernia. The morphological description of the EGJ by EPT has also revealed not only a spectrum of abnormality ranging from an intact sphincter to overt herniation but also the surprise finding of spontaneous conversion among sphincter configurations emphasizing its dynamic nature. Finally, with respect to barrier function, preliminary data have refocused on the CD as a key differentiating feature between preserved and compromised function.
Although the accomplishments summarized in the previous section are substantial, much work remains to fully exploit the potential of EPT in the clinical characterization of the EGJ. In particular, the significance of morphological subtypes and CD function as they pertain to GERD has only barely been explored. GERD is the major cause of upper gastrointestinal morbidity in Western society and it is fundamentally a physiological disturbance of the EGJ. Nonetheless, prior to the introduction of HRM, the manometric evaluation of the EGJ provided minimal insight into characterizing its dysfunction. This robust technology, and future evolutions thereof, surely will finally reveal some of these secrets.
PJK is supported by R01 DK56033 and R01 DK079902 from the US Public Health Service.
There are no financial or professional disclosures relevant to the synthesis of this paper for either of the authors.
PJK performed the initial literature search, wrote the initial draft of the paper and managed the integration of coauthor contributions; JHP assisted in critiquing, editing, and refining the paper.