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Keywords:

  • 3D high-resolution manometry;
  • esophageal impedance planimetry;
  • high frequency esophageal endoscopic ultrasound;
  • high-resolution impedance manometry;
  • high-resolution manometry

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in Manometry: From Motility to Function
  5. Future Directions in Manometry: From Function to Symptoms
  6. Future Directions: Beyond HRM
  7. Conclusion
  8. Acknowledgments
  9. References

Background  Symptom based diagnosis is not reliable in patients with swallowing problems, heartburn, and other dyspeptic complaints. The aim of investigation is to provide clinically relevant measurements of gastrointestinal structure and function that explain the cause of symptoms, identify pathology, and guide effective management. Current practice rarely meets these ideals.

Purpose  This review considers recent advances in technology such as high-resolution manometry (HRM) with esophageal pressure topography (EPT), HRM with impedance, high frequency ultrasound, and endoscopic functional luminal impedance planimetry (Endo-FLIP) that provide new opportunities to identify the pathophysiologic basis of esophageal symptoms and disease. As experience with these new devices increases researchers are developing new methodologies that maximize their utility in clinical practice. For example, application of HRM to assess motility and function during and after a test meal can identify the causes of swallowing problems, reflux and other postprandial symptoms and intra-operative application of Endo-FLIP may help surgeons perform antireflux surgery. These examples illustrate the potential of physiologic measurement to direct rational and effective clinical management for individual patients.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in Manometry: From Motility to Function
  5. Future Directions in Manometry: From Function to Symptoms
  6. Future Directions: Beyond HRM
  7. Conclusion
  8. Acknowledgments
  9. References

Symptom based diagnosis is not reliable in patients with swallowing problems, heartburn and other dyspeptic complaints.1,2 The aim of investigation is to provide clinically relevant measurements of gastrointestinal (GI) structure and function that explain the cause of symptoms, identify pathology, and guide effective management.3,4 Current practice rarely meets these ideals. Once ‘organic disease’ has been ruled out by laboratory tests, endoscopy and imaging, guidelines recommend assessment of upper GI physiology.5,6 Unfortunately, in many patients, manometry with 5–8 pressure sensors and reflux studies also fail to establish a definitive diagnosis.3,7 In such cases diagnoses such as ‘functional dysphagia’ or ‘functional heartburn’ are applied. This is not helpful to the patient or doctor because these labels are nonspecific and simply reflect the presence of symptoms and the absence of objective findings on investigation. No insight into the pathophysiologic basis of disease is given. Furthermore, such labels may imply psychological disease and provide little direction for therapeutic decisions.

Advances in Manometry: From Motility to Function

  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in Manometry: From Motility to Function
  5. Future Directions in Manometry: From Function to Symptoms
  6. Future Directions: Beyond HRM
  7. Conclusion
  8. Acknowledgments
  9. References

Recent advances in physiologic measurement such as high-resolution manometry (HRM) with esophageal pressure topography (EPT) provide a new opportunity to move beyond symptom based diagnosis in functional GI disease. A key insight from studies that combined conventional manometry with impedance is that esophageal symptoms are rarely caused by dysmotility unless this is accompanied by bolus retention or reflux.8,9 This approach changed the terminology of ‘non-specific esophageal dysmotility’ to ‘ineffective esophageal motility’ and allowed these disorders to be stratified in terms of their impact on bolus transport;8,9 however, this method still did not explain the causes of dysfunction. In contrast, HRM/EPT with closely spaced sensors provides sufficient spatial resolution to assess not only contractile force (motility) but also the forces that drive the movement of fluid and food (function).10 The presence of well coordinated peristaltic contraction without wide breaks in the contractile front from the pharynx to the stomach defines whether or not esophageal motility is normal. The presence of a positive intra-bolus pressure (IBP) gradient across the esophago-gastric junction (EGJ) defines whether or not this motility is consistent with effective function.3

The Chicago Classification presented in this supplement11 represents an important advance because it is built on these physiomechanical principles. The system is hierarchical with EGJ dysfunction considered first because failure of the EGJ to relax and/or open in achalasia and outflow obstruction has a greater impact on bolus transport than abnormal peristalsis.12 In addition, it makes a clear distinction between dysmotility and dysfunction that is ‘never seen in normal individuals’ from that which is merely ‘outside the normal range’. In the former there is a clear rationale for treatment directed at correcting the pathology. In the latter symptoms are likely to be associated with both esophageal motor dysfunction and visceral hyperalgesia or hypervigilance.13,14

Systematic analysis of HRM/EPT data increases diagnostic accuracy in large case series.15,16 In particular, attention to breaks in the contractile front detects functionally relevant segmental dysmotility not visualized by other methods4,17 and the IBP gradient detects functional EGJ outlet obstruction.15,16,18,19 This approach has implications for the design of outcome studies. In achalasia three distinct patterns of aperistalsis are discernable with HRM/EPT that predict responsiveness to therapy.20 Studies have also defined specific ‘clinical phenotypes’ of hypotensive21 and hypertensive esophageal dysmotility22 that may respond to specific interventions.23,24

Future Directions in Manometry: From Function to Symptoms

  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in Manometry: From Motility to Function
  5. Future Directions in Manometry: From Function to Symptoms
  6. Future Directions: Beyond HRM
  7. Conclusion
  8. Acknowledgments
  9. References

Despite the technical advances set out above, standard methodologies using HRM/EPT still fail to establish a definitive diagnosis that explains the cause of symptoms in many patients with swallowing problems or reflux.4,25 This may be because it does not provide a direct assessment of esophageal shortening, sensitivity or certain other biomechanical properties (see below). Alternatively it may be because tests based on small volume water swallows in the supine position are not representative of normal behavior and/or do not ‘challenge’ esophageal function. High-resolution manometry/ Esophageal pressure topography can facilitate the assessment of complex pressure activity that occurs during normal drinking and eating in the physiologic upright, seated position (Fig. 1). Specifically, in healthy volunteers, the esophagus responds to solids by increasing coordination and vigor of peristaltic contraction.26 Similar results are found in patients with mild-moderate reflux disease but not in more severe disease (Fig. 2). Interestingly, although hypotensive dysmotility is common with water swallows in both groups, only failure to respond to the ‘challenge’ of bread swallows is associated with poor clearance and increased acid exposure on ambulatory pH-studies, and the presence of erosive esophagitis on endoscopy.27 This is a novel observation; however, the major impact of including free drinking [multiple water swallows (MWS)] and solids in clinical studies may be to provoke esophageal dysfunction and symptoms (Fig. 3).28,29 The introduction of high-resolution impedance manometry (HRIM) is valuable in this context because impedance provides a direct assessment of bolus transport that confirms the functional effects of the complex pressure data that is observed during normal drinking and eating behavior (Fig. 4).30 Demonstration of a close temporal association between ‘abnormal pressure events’, bolus retention and typical patient symptoms on multiple occasions during a test meal provides strong support for the clinical relevance of these ‘events’. Symptom association analysis in ambulatory reflux studies provides a direct explanation for patient symptoms31 that can guide effective management.32,33 Ambulatory HRM is not, as yet, available; however, this may not be essential because swallowing problems take place almost exclusively during meals. Certainly, case reports and initial findings from case series in patients with functional dysphagia suggest that this approach increases diagnostic sensitivity to symptomatic esophageal dysfunction.3,4,28

image

Figure 1.  Examples of HRM studies of swallowing function from healthy subjects. Note how the esophagus responds to increasing esophageal workload by improving coordination and increasing the power of contraction (upper panel of figures, moving from liquid swallows in the upright position to solid swallows lying down). On drinking 200 ml water, esophageal contractility is suppressed during repeated swallowing and there is no sign of outlet obstruction (i.e. no intra-bolus pressure gradient across the EGJ) and this is followed by a powerful contraction that clears the esophagus (lower left figure). Powerful contractions are observed also during a solid test meal (lower right figure); however, these are interspersed with occasional failed swallows and spasm. These ‘abnormalities’ do not cause symptoms unless several ineffective swallows occur one after another.

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image

Figure 2.  Representative HRM/EPT from water and solid swallows in patients with non-erosive (above) and erosive reflux disease (below). Peristaltic function following water swallows is ineffective with wide (>3 cm) separation of proximal and mid-distal esophageal contractions in both patients. In contrast, there is an ‘effective peristaltic response’ to solid swallows only in the patient with non-erosive disease. Failure to respond to physiologic challenge characterizes esophageal motility in erosive gastro-esophageal reflux disease. ENRD = Endoscopy negative reflux disease; ERD = Erosive reflux disease. Note also the presence of a small hiatus hernia in the patient with erosive disease. Reproduced with permission from Daum et al. Neurogastroenterol Motil 2011.27

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image

Figure 3.  Representative swallows from a patient with dysphagia, regurgitation of food and weight loss with normal endoscopy. (A) Single water swallow is normal. (B, C) Single solid swallow shows variable peristaltic response but consistent evidence of outlet obstruction [raised intra-bolus pressure (IBP)]. Typical symptoms were reproduced. Endoscopic ultrasound identified a submucosal tumor at the EGJ. EGJ = Esophago-gastric junction; (D) MWS = Multiple water swallows.

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image

Figure 4.  Representative swallows during a test meal from a patient with dysphagia and regurgitation. Water swallows showed normal motility. With solid swallows diffuse and segmental esophageal spasm was present. Impedance demonstrated that in this case these events caused proximal bolus retention and were not an effect of bolus obstruction [dysmotility can be the cause or the effect of such events30]. The patient reported dysphagia when this was present. Note how the solid bolus is cleared by free drinking. MWS = Multiple water swallows.

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The Chicago Classification is focused on peristaltic dysfunction and EGJ outlet obstruction; however, the majority of patients referred for physiologic studies complain of reflux symptoms. Stationary HRM/EPT studies detail the structure and function of the reflux barrier;34,35 however, standard parameters such as LES pressure and length have not been included in the current system because their association with acid exposure on ambulatory studies is weak (Fig. 2).35 New ‘3D HRM’ technology provides even more detail than standard HRM, revealing the functional anatomy of the EGJ anatomy, especially the contribution of the crural diaphragm (Fig. 5).36 Notwithstanding these insights, in the absence of gross disruption (i.e. hiatus hernia) baseline measurements are not able to predict the presence of severe reflux or the likelihood of reflux related symptoms. GERD diagnosis requires ambulatory pH ± impedance studies; however, postprandial manometric studies can provide insights into the mechanism of disease. HRM accurately detects transient and swallow related lower esophageal sphincter relaxations (TLESR and SLESR), intermittent separation of the intrinsic and extrinsic components of the EGJ, straining, rumination and other events that can result in the return of gastric contents to the esophagus and mouth (Fig. 6).16,37–39 High-resolution manometry /Esophageal pressure topography can predict and HRIM can document whether or not these events are associated with reflux of liquid or gas (belching). These observations explain the cause of symptoms and have the potential to direct specific medical, behavioral, and surgical treatment.

image

Figure 5.  3D HRM acquires detailed pressure measurement across the EGJ with 96 independent solid-state pressure sensors (axial spacing 0.75 cm, radial spacing 45 degrees over 7.5 cm). The functional anatomy of the reflux barrier is revealed as shorter than that with conventional HRM and profoundly asymmetric with the vigorous crural component to EGJ pressure superimposed on the LES. EGJ = Esophago-gastric junction. Reproduced with permission from Kwiatek et al. Neurogastroenterol Motil 2010.36

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image

Figure 6.  Rumination during postprandial observation period in a patient referred for investigation of ‘vomiting’ after meals that had been resistant to all medical therapy. On eating, the patient complained of dyspeptic symptoms, and then abdominal contractions were observed which forced gastric contents into the esophagus and back to the mouth. The patient then swallowed. Rumination is a voluntary, albeit subconscious, learned behavior. This patient responded after only one session of biofeedback therapy.

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Future Directions: Beyond HRM

  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in Manometry: From Motility to Function
  5. Future Directions in Manometry: From Function to Symptoms
  6. Future Directions: Beyond HRM
  7. Conclusion
  8. Acknowledgments
  9. References

Several important biomechanical properties of the esophagus and EGJ cannot be assessed by manometry. Contraction of the longitudinal muscle layer is required for effective peristaltic contraction and normal EGJ relaxation. This cannot usually be detected by pressure measurement but is visualized by high frequency endoscopic ultrasound. This technique detects impaired coordination between the longitudinal and circular muscle in some patients with esophageal dysfunction.40 Moreover, esophageal shortening due to ‘longitudinal spasm’ has been associated with chest pain and other symptoms.41,42 However, the clinical relevance of these events is not certain because dramatic esophageal shortening can often be seen by the movement of radio-opaque clips on videofluoroscopy during TLESRs without symptoms.43

Esophageal distensibility and sensitivity can be assessed by impedance planimetry, a technique that measures cross-sectional area of the esophagus in response to distension. In a recent case series, abnormal esophageal stiffness and visceral hyperalgesia to distension was found in 143/189 (75%) patients with ‘functional chest pain’ in whom conventional manometric and pH-studies were normal. Typical symptoms were reproduced in 105 (56%) subjects.44 These findings suggest that treatment directed at relaxing the esophageal wall and reducing esophageal sensitivity may be targets for treatment in this patient group. Esophageal sensitivity can be assessed also using electricity, temperature, infusion of acid, and other chemicals; however, distension is a clinically relevant stimulus in patients with dysmotility and/or PPI resistant GERD and no other technique has shown comparable results in clinical studies.

Esophago-gastric junction distensibility can also be measured by impedance planimetry (Endo-FLIP®; Crospon Medical Devices, Galway, Ireland).45 This technique has confirmed that the EGJ is more distensible (i.e. opens more easily) in GERD patients than healthy controls and that this property is normalized after fundoplication (Fig. 7).46 The utility of this device in GERD diagnosis is not certain; however, there is considerable interest in its use as a ‘clever bougie’ in anti reflux surgery to ensure that hiatal repair and fundoplication wrap form a reflux barrier that is neither too ‘loose’, nor too ‘tight’.47 In addition, Endo-FLIP® can identify and quantify outlet obstruction at the EGJ due to complications or a ‘tight’ repair after antireflux surgery, achalasia and also in other conditions such as eosinophilic esophagitis.48

image

Figure 7.  The Endo-FLIP® system monitors the cross-sectional diameter of a bag with a series of impedance electrodes and pressure transducers along its length during a sequence of volumetric distensions. The bag is placed across the EGJ and, typically, an hourglass shape is observed. The examples illustrate the greater EGJ distensibility with larger hiatal diameter and lower intra-bag pressures at 20–40 ml distension volumes in a GERD patient compared to control. EGJ = Esophago-gastric junction Reproduced with permission from Kwiatek et al. J Gastrointest Surgery 2010.46

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Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in Manometry: From Motility to Function
  5. Future Directions in Manometry: From Function to Symptoms
  6. Future Directions: Beyond HRM
  7. Conclusion
  8. Acknowledgments
  9. References

The success of scientific medicine is based on the identification and treatment of the pathophysiological basis of disease. In the past management options in functional esophageal disease have been limited; however now, as in many other areas of medicine, technology is driving progress. New instruments are available to assess every aspect of esophageal motor and sensory function. In addition, new methodologies with application of HRM/EPT and, in particular, HRIM to assess motility and function during and after a test meal can identify the causes of swallowing problems, reflux, and other postprandial symptoms. This information has the potential to direct personalized clinical management.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in Manometry: From Motility to Function
  5. Future Directions in Manometry: From Function to Symptoms
  6. Future Directions: Beyond HRM
  7. Conclusion
  8. Acknowledgments
  9. References

Mark Fox and Rami Sweis contributed to and approved the manuscript. Mark Fox and the HRM Working Group are grateful to the academic and industry sponsors of the ‘Advances in Clinical Oesophageal Measurement’ conference, Ascona 10–15. April 2011: The University of Zurich and the Swiss Federal Institute of Technology Zurich, Centro Stefano Franscini, United European Gastroenterology Foundation, Given Imaging/Sierra Scientific Instruments, Medical Measurement Systems and Sandhill Scientific Instruments.

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  1. Top of page
  2. Abstract
  3. Introduction
  4. Advances in Manometry: From Motility to Function
  5. Future Directions in Manometry: From Function to Symptoms
  6. Future Directions: Beyond HRM
  7. Conclusion
  8. Acknowledgments
  9. References
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