The mechanical properties of the esophagogastric junction (EGJ) are of major importance for the competence of the EGJ. Although manometry reliably measures sphincter pressure, no information is provided on distensibility, a crucial determinant of flow across the EGJ. Recently, a new technique, impedance planimetry, was introduced allowing accurate measurement of compliance or distensibility. This review discusses the recent advances in this area and highlights the clinical relevance of this new technique evaluating the mechanical properties of the esophageal wall and EGJ.
Key points
- •
Impedance planimetry allows accurate measurement of compliance or distensibility.
- •
Distensibility is a better parameter than pressure alone to evaluate sphincter competence.
- •
Distensibility of the esophagogastric junction (EGJ) is increased in gastroesophageal reflux disease patients and normalized by fundoplication.
- •
Untreated achalasia patients have a lower distensibility of the EGJ than well-treated achalasia patients and healthy volunteers.
- •
In achalasia, EGJ distensibility correlates with symptom severity and may therefore play a potentially important role in the clinical management of achalasia.
- •
Functional lumen imaging probe technology may provide valuable perioperative information on EGJ distensibility during Heller myotomy, peroral endoscopic myotomy, and antireflux surgery.
Introduction
The esophagus is a muscular tube, serving as a conduit between the oral cavity and the stomach with its principle role to transport ingested material toward the stomach. At its distal end, the lower esophageal sphincter (LES) is continuously contracted to prevent reflux of gastric contents. Sphincter competence and more specific competence of the esophagogastric junction (EGJ) involve a complex interaction between LES tone, diaphragmatic contraction during the respiratory cycle, and the valvular effect caused by the sling fibers. More than 40 years ago, Harris and Pope identified that resistance to distension by measurement of radial force rather than sphincter pressure should be the prime determinant of sphincteric strength. Hence, measuring pressure and cross-sectional areas (CSA) of the EGJ would be a better parameter to evaluate sphincter competence. Conversely, transport of intraluminal contents across the EGJ is largely determined by the diameter of the EGJ. Pandolfino and colleagues indeed elegantly demonstrated that volume flow across the EGJ can be estimated by using a simplified mathematical model based on Newton’s law of motion. From this model, it is evident that flow is highly dependent on the diameter of the EGJ, given that it is factored to the 4th power in the equation of the mathematical model. Based on these findings, it is becoming increasingly clear that not basal pressure generated by the EGJ but rather its ability to open or distend is the main determinant of flow, in either antegrade or retrograde direction. Hence, clinical tools measuring distensibility may prove to be more useful to assess the function of the EGJ.
Introduction
The esophagus is a muscular tube, serving as a conduit between the oral cavity and the stomach with its principle role to transport ingested material toward the stomach. At its distal end, the lower esophageal sphincter (LES) is continuously contracted to prevent reflux of gastric contents. Sphincter competence and more specific competence of the esophagogastric junction (EGJ) involve a complex interaction between LES tone, diaphragmatic contraction during the respiratory cycle, and the valvular effect caused by the sling fibers. More than 40 years ago, Harris and Pope identified that resistance to distension by measurement of radial force rather than sphincter pressure should be the prime determinant of sphincteric strength. Hence, measuring pressure and cross-sectional areas (CSA) of the EGJ would be a better parameter to evaluate sphincter competence. Conversely, transport of intraluminal contents across the EGJ is largely determined by the diameter of the EGJ. Pandolfino and colleagues indeed elegantly demonstrated that volume flow across the EGJ can be estimated by using a simplified mathematical model based on Newton’s law of motion. From this model, it is evident that flow is highly dependent on the diameter of the EGJ, given that it is factored to the 4th power in the equation of the mathematical model. Based on these findings, it is becoming increasingly clear that not basal pressure generated by the EGJ but rather its ability to open or distend is the main determinant of flow, in either antegrade or retrograde direction. Hence, clinical tools measuring distensibility may prove to be more useful to assess the function of the EGJ.
Earlier methods to measure distensibility
In 2002, Pandolfino and colleagues elegantly combined distension of the EGJ using a barostat balloon with barium swallow images to assess the EGJ distensibility. The balloon pressure was set at 5 mm Hg and was subsequently increased in 2-mm Hg increments until opening of the EGJ was noted fluoroscopically. In addition, the diameter of the EGJ was assessed during 5-mL dilute barium swallows at different barostat balloon pressures. Distensibility was then defined as the relationship between the EGJ diameter (measured by barium swallow) and balloon distension pressure. This technique was performed in 8 healthy volunteers and 9 reflux patients with a hiatal hernia. The distensibility of the EGJ was significantly increased in gastroesophageal reflux disease (GERD) patients with a hiatus hernia such that the opening occurred at a significantly lower distension pressure and that for a given distention pressure the resultant opening diameter was on average 0.5 cm wider.
The underlying hypothesis for measuring the compliance of the EGJ during LES relaxation was that the observed increased diameters in hernia patients would both qualitatively and quantitatively determine retrograde gastroesophageal flow. Using a mathematical model based on Newton’s law of motion, it is indeed evident that flow is highly dependent on diameter, given that it is factored to the 4th power. Furthermore, using this model together with the pressure and diameter measurements described above, estimations for esophagogastric flow across the EGJ for water and air were made for healthy volunteers as well as GERD patients with a hiatal hernia. The flow for either air or water was 2-fold to 3-fold greater for the hernia group compared with normal subjects at each value of gastroesophageal pressure gradient. Within each group, flow of air is about 2 orders of magnitude greater than the flow of water. Thus, the lower opening pressure and 0.5-cm increase in EGJ diameter observed in hernia patients coupled with the difference in viscosity between water and air make a normal individual capable of venting large volumes of gas from the stomach at low pressure with minimal potential for liquid reflux, whereas hernia patients will vent large volumes of air or water at similar pressures. A correlate of this is that the volume of refluxate is also uniformly higher among hernia patients. Taken together, this study of Pandolfino showed that measuring opening patterns and distensibility can be an indicator of the status of the junction in health or disease. However, this early method using barostat and fluoroscopy is cumbersome because it involves radiation and therefore is not suitable for clinical practice.
Principle of impedance planimetry
In 1971, Harris and colleagues described a method to assess the CSA of the ureter using impedance measurements between 4 different electrodes placed on a thin probe. It took another 10 years, however, before Colstrup and colleagues developed an expandable nonconductible balloon containing electrodes, allowing the measurement of biomechanical wall properties. This technique is based on the principle that the CSA is inversely proportional to the voltage across the sensing electrodes if a current passes through a polyurethane bag filled with saline. If all other parameters are kept constant, the impedance is proportional to the CSA of the bag between the sensing electrodes ( Fig. 1 ).
In contrast to the barostat, whereby distension data are based on pressure-volume relationships, impedance planimetry enables actual measurement of CSA during balloon distension, which correlates better to diametrical changes in the digestive lumen. Although several studies have validated the use of impedance planimetry in the esophagus of healthy volunteers and patients, few studies have been performed in sphincter regions due to several technical limitations. First, accurate positioning of the electrode in the sphincteric region is rather difficult. Second, there is a tendency for bag displacement during distension in a high pressure zone such as a sphincter. To overcome this, a multielectrode probe has been created allowing the simultaneous recording of CSA at different positions. McMahon and colleagues proved that this multielectrode technique is indeed capable of generating an illustration of the geometric changes in the EGJ, thereby profiling the lumen of the organ under study. This probe is known as the functional lumen imaging probe (FLIP), which has recently become commercially available (endoFLIP; Crospon Medical Divices, Galway, Ireland). It consists of a 240-cm-long catheter with a 14-cm bag, compliant to a maximal diameter of 25 mm, attached to its distal end. Inside the bag, 17 electrodes are placed at 4-mm intervals. An excitation current of 100 μA is generated between 2 adjacent electrodes at a frequency of 5 kHz. Using impedance planimetry, CSAs are determined for the 16 cross-sections during volume-controlled distensions. In addition, 2 pressure sensors determine intrabag pressure, allowing assessment of EGJ distensibility ( Fig. 2 ).
Functional luminal imaging and EGJ disease
Healthy Volunteers
It is clear from several studies that FLIP measurement can be performed easily and safely. It can be performed during endoscopy or as a separate procedure; in either case, the FLIP probe is mostly well tolerated. Kwiatek and colleagues performed a study in 20 healthy volunteers. The FLIP procedure was performed during a routine esophagogastroduodenoscopy, where the FLIP probe was passed through the endoscopic instrumentation channel and positioned across the EGJ. All patients received moderate sedation during the procedure (5–15 mg midazolam, 20–200 μg fentanyl). In healthy volunteers, a mean CSA of 94 (27–225) mm 2 was measured at the 30 mL distension of the FLIP bag and a mean CSA of 264 (99–496) mm 2 was seen at the 40 mL distension, corresponding with an intrabag pressure of 25 (6–47) and 39 (17–60) mm Hg, respectively. EGJ distensibility (CSA vs pressure) was based on the narrowest CSA and the corresponding intrabag pressure and expressed as the EGJ distensibility index (DI) at each distention volume. The index was calculated as [narrowest CSA/(intrabag pressure + intragastric pressure offset)], wherein intragastric pressure was given as 4.0 mm Hg based on previous reports of typical normal intragastric pressure values across healthy controls. The DI was 4 (1–14) mm 2 /mm Hg at the 30 mL distension and 6 (4–8) mm 2 /mm Hg at the 40 mL distension.
The study of Rohof and colleagues confirmed these results. In this study, 15 healthy volunteers were studied. The FLIP procedure was performed as a separate procedure, without sedation. Healthy volunteers had a mean EGJ distensibility of 6.3 ± 0.7 mm 2 /mm Hg using a 50-mL volume distension.
GERD
GERD is one of the most common digestive diseases in the Western world, resulting from repetitive exposure of the esophagus to gastric contents. Given the high prevalence of GERD, understanding of the pathophysiology is of great importance. In the following section, the evidence indicating that increased EGJ compliance is one of the pathophysiological abnormalities contributing to increased esophageal acid exposure is reviewed.
Functional measurement
Currently, EGJ distensibility measurement is mostly performed using a commercially developed device (ie, the EndoFLIP). This probe consists of a 240-cm-long catheter with a 14-cm balloon attached to its distal end positioned in the esophagus with the impedance electrodes straddling the EGJ at the center of the balloon. In most distension protocols, the balloon is inflated to a 20-mL, 30-mL, 40-mL, and 50-mL volume. Pressures and CSAs are collected at a rate of 10 Hz. Distensibility is assessed using the median value over a 30-second dynamic measurement of the narrowest CSA, which corresponds to the EGJ, and the median intrabag pressure.
Kwiatek and colleagues measured EGJ distensibility in 20 healthy volunteers and 20 GERD patients without hiatal hernia. In both groups, the least distensible locus at the EGJ was usually at the hiatus. As a group, GERD patients exhibited 2-fold to 3-fold increased EGJ distensibility compared with controls, particularly at 20-mL to 30-mL distention volumes. These values are quantitatively similar to the previous measurements using barostat balloon distension of the EGJ. However, these findings could not be confirmed in the study of Tucker and colleagues. In this study, 22 healthy volunteers and 18 GERD patients were included, surprisingly showing that patients with reflux symptoms had a lower CSA and distensibility than healthy volunteers. A possible explanation for this controversy could be the difference in control group used, given that 14% of the healthy volunteers had a pathologic acid exposure on wireless pH monitoring.
As an increased distensibility is part of the underlying pathophysiological abnormalities in GERD, efficient treatment should aim to correct this abnormality. Indeed, Blom and colleagues showed a significant reduction of distensibility after antireflux surgery. Distensibility was determined in 15 patients who underwent Nissen fundoplication using custom-made catheter before and after surgery with the patient under general anesthesia. These results are in line with the earlier barostat study of Pandolfino. In this study, EGJ opening pressure and opening diameter after fundoplication were decreased to levels similar to normal subjects.
Intraoperative measurement
Laparoscopic Nissen fundoplication is the surgical treatment of choice for GERD. However, this procedure may be associated with complications, such as dysphagia, gas bloat, and inability to belch and vomit, as a result of a too-tight fundic wrap. Therefore, intraoperative measurement of distensibility could possibly guide the surgeon to determine the optimal size of the fundic wrap, thereby preventing or reducing the risk of these postoperative complications. Ilczyszyn and Botha studied the feasibility of intraoperative distensibility measurement using the FLIP probe. Intraoperative FLIP measurement was performed in 17 subjects without perioperative and postoperative complications. Hiatus repair and fundoplication result in a significant overall reduction in the median distensibility at 30-mL and 40-mL distensions (30-mL balloon distension reduction of 3.26 mm 2 /mm Hg [ P = .0087], 40 mL balloon distension reduction of 2.39 mm 2 /mm Hg [ P = .0039]). Of interest, intraoperative distensibility was very low (0.47 mm 2 /mm Hg) in one patient, who subsequently required reoperation because of significant symptoms of dysphagia. Another patient in the series had a fundoplication that appeared visually too tight. FLIP measurement showed a low DI of 0.65 mm 2 /mm Hg. Based on this FLIP measurement, the procedure was converted intraoperatively to a Lind 270° wrap, resulting in a change in the DI from 0.65 to 0.89 mm 2 /mm Hg. Afterward, this patient had no symptoms of dysphagia. These data elegantly show that the EndoFLIP system could be useful to help the surgeon construct the optimal fundic wrap. Further studies are needed to confirm improved clinical results and reduction of postoperative dysphagia or gas bloat following antireflux surgery when combined with intraoperative assessment of EGJ distensibility.
Achalasia
Achalasia is the best characterized esophageal motility disorder. It is caused by disappearance of inhibitory neurons leading to a loss of peristalsis and defective relaxation of the LES. The subsequent retention of food in the esophagus results in the typical symptoms of achalasia (ie, dysphagia, regurgitation of undigested food, chest pain, and weight loss). As the neuronal loss is irreversible, there is no curative treatment of achalasia. Although the pathophysiology of achalasia is associated with impairment of both peristalsis and LES relaxation, treatment is focused on reducing EGJ pressure to improve bolus passage and thereby ameliorating symptoms. Recent insight, however, revealed that not only basal sphincter pressure but also distensibility of the EGJ is a major determinant of esophageal emptying and thus therapeutic success. Indeed, Rohof and colleagues showed that compliance was significantly reduced in untreated achalasia patients and patients with recurrent symptoms compared with controls and that distensibility was increased after treatment. Moreover, in patients with achalasia, EGJ distensibility correlates with esophageal emptying and symptoms. Therefore, impedance planimetry can be of use in the management of achalasia.
Intraoperative measurement
Current treatment modalities to lower LES tone consist of pneumatic dilation, laparoscopic Heller myotomy (LHM), and peroral endoscopic myotomy (POEM). Surgical treatment of achalasia involves myotomy of the LES; however, it remains difficult for the surgeon to estimate the completeness of the myotomy. The same applies to the most recently introduced treatment of achalasia (ie, POEM). During POEM, a submucosal tunnel is created during endoscopy to reach the LES and to dissect the circular muscle fibers over a 7- to 10-cm esophageal and 2-cm gastric length.
As the completeness of the myotomy is not always easy to assess, some investigators have tried to improve surgical success rates by measuring the residual LES pressure using perioperative manometry. Of interest, manometry could indeed identify persistent high pressure zone, suggestive of incomplete myotomy, that could be corrected during surgery with further section of circular muscle fibers.
In line, endoFLIP has been used as an adjunctive guide during Heller myotomy or POEM. Teitelbaum and colleagues recently published the results of perioperative distensibility changes measured by FLIP in 29 patients who underwent LHM or POEM. FLIP could be performed intraoperatively in 86% of patients showing a significant increase in CSA at 40-mL FLIP distension after myotomy in LHM and POEM. In addition, intrabag pressure decreased significantly after POEM (mean pre 34 ± 9.5 mm Hg vs mean post 21.8 ± 6.2 mm Hg; P <.001), whereas LHM resulted only in a trend toward decreased intrabag pressure at a 40-mL distension volume (mean pre 32.4 ± 14.1 mm Hg vs mean post 25 ± 9.5 mm Hg; P = .08). The DI increased significantly following LHM (mean pre 1.4 ± 1.3 mm 2 /mm Hg vs mean post 7.6 ± 4.4 mm 2 /mm Hg; P <.001). POEM led to a similar increase (mean pre 1.4 ± 1.9 mm 2 /mm Hg vs mean post 7.9 ± 2.7 mm 2 /mm Hg; P <.001).
These data illustrate that intraoperative recording of distensibility is feasible with FLIP and that both LHM and POEM result in a comparable 4-fold to 5-fold increase in distensibility. Most interestingly, these studies show that intraoperative FLIP has the potential to be used during LHM and POEM to calibrate the myotomy and fundoplication, and to ensure an adequate release of the EGJ.
Functional measurement
With regard to the clinical management of achalasia, it is important to identify patients in need of re-treatment to prevent long-term complications, such as dilatation of the esophagus and increased risk to develop dysplasia. Identification of these patients is often challenging because symptoms do not correlate with functional parameters, mainly because patients get used to symptoms and adapt their diet accordingly. Therefore, objective functional markers evaluating the EGJ are needed. Several studies have proposed manometry to be a useful test to determine whether patients should be re-treated. In general, LES pressure lower than 10 mm Hg after therapy has been reported to be a good predictor of treatment success. However, other studies and clinical experience contradict these results, especially because a significant proportion of patients have persistent symptoms despite low LES pressure. Interestingly, these patients have incomplete esophageal emptying on a timed barium esophagogram, while a significant proportion of these patients benefit from additional treatment with pneumodilation. These observations argue against LES pressure as a useful test to assess the need for treatment. Recent findings suggest that assessment of distensibility may represent a better approach to identify patients in need of re-treatment. FLIP data indeed correlated better with esophageal emptying and clinical response compared with manometry ( Fig. 3 ). Rohof and colleagues showed that EGJ distensibility was significantly reduced in untreated patients with achalasia, compared with controls (0.7 ± 0.9 mm 2 /mm Hg vs 6.3 ± 0.7 mm 2 /mm Hg; P <.001) and that EGJ distensibility correlated with esophageal emptying ( r = –0.72; P <.01) and symptoms ( r = 0.61; P <.01). Moreover, distensibility was significantly increased with treatment and was significantly higher in patients successfully treated (Eckardt score <3) compared with those having persistent symptoms (1.6 ± 0.3 vs 4.4 ± 0.5 mm 2 /mm Hg, respectively, P = .001). Furthermore, a cutoff value for treatment success and failure was determined. A value of less than 2.9 mm 2 /mm Hg at the 50-mL distension indicated treatment failure with a sensitivity of 92% and a specificity of 72% ( Fig. 4 ). Pandolfino and colleagues confirmed these findings in 20 healthy volunteers and 54 achalasia patients. The esophagogastric junction-distensibility index (EGJ-DI) was greatest in control subjects and least in the untreated patients; patients with a good treatment response had significantly greater EGJ-DI than untreated patients or patients with a poor treatment response.
