Crural Diaphragm Research Articles

Sa1105 - P-Akt/Akt Pathways in the Crural Diaphragm are Involved in the Pathogenesis of Reflux Esophagitis in Humans — a Preliminary Report

Sa1105 - P-Akt/Akt Pathways in the Crural Diaphragm are Involved in the Pathogenesis of Reflux Esophagitis in Humans — a Preliminary Report

Sa1104 - P-Akt/Akt Pathways in the Crural Diaphragm are Involved in the Pathogenesis of Reflux Esophagitis in Rats

Sa1104 - P-Akt/Akt Pathways in the Crural Diaphragm are Involved in the Pathogenesis of Reflux Esophagitis in Rats

Манометрия высокого разрешения в клинической практике: анализ двигательной функции пищевода в соответствии с Чикагской классификацией

Aim of review. To analyze the basic esophageal pressure metrics according to Chicago classification v3.0, received at high-resolution manometry and to present the results of clinical application. Summary. Nowadays high-resolution manometry is the most exact hi-tech diagnostic method for esophageal motor function disorders. The changes identified during the investigation are systematized in the Chicago classification v3.0. This relatively new diagnostic method was introduced to clinical application in Russian Federation for the first time in 2011. Vasilenko clinic of internal diseases propedeutics, gastroenterology and hepatology (Sechenov University) accumulated significant experience of high-resolution esophageal manometry of overall 1150 studies. Uniqueness of the method consists in capacity to define integrated quantitative and qualitative metrics of esophageal contractile function and to establish their specific disorders e.g.: change of intrabolus pressure at disorders of esophagogastric junction (EGj) outflow, hypercontractile esophagus, fragmented contractions and weak or failed peristalsis, distal esophageal spasm. Assessment of the type of achalasia subtypes has significant impact on the patients’ treatment choice. Differential diagnosis of belching type, rumination, aerophagy became possible at combined application of high-resolution manometry and impedance measurement. According to anatomical location of the lower esophageal sphincter and crural diaphragm several morphological types of gastro-esophageal junction are defined that determine severity of gastroesophageal reflux disease. Additional provocative tests can be recommended prior to considering anti-reflux surgical treatment that will help to forecast the risk of complications. High-resolution manometry is indicated for patients presenting with dysphagia symptoms, noncoronary chest pain, gastroesophageal reflux disease and other disorders. Conclusion. High-resolution manometry is a fundamental diagnostic test of esophageal motor function disorders. Clinical application of this method significantly expands diagnostic potential and allows to carry out personalized treatment that increases treatment quality.

Correlation between novel 3D high-resolution manometry esophagogastric junction metrics and pH-metry in reflux disease patients.

We recently developed 2 novel 3D high-resolution manometry (HRM) metrics of esophagogastric junction (EGJ) contractility to differentiate the lower esophageal sphincter (LES) and crural diaphragm (CD) elements of EGJ pressure. This study aimed to compare these metrics to the EGJ-contractile integral (EGJ-CI) and to analyze their correlation with esophageal acid exposure time (AET) on pH-metry. Thirty-one gastro-oesophageal reflux disease (GERD) patients and 20 control subjects underwent 24-hour pH-metry and HRM using a 3D-HRM catheter. EGJ metrics were calculated during 3 consecutive respiratory cycles at rest. The EGJ-CI was calculated using the DCI tool in the ManoView software. 3D LES pressure (3D-LESP) and 3D-DHA, a metric quantifying the CD component of the 3D-HRM pressure topography, were calculated using a MATLAB program. Pearson correlation was used to calculate correlations with AET. 3D-LESP, 3D-DHA, and EGJ-CI were all significantly lower in GERD patients than in control subjects (P<.05) and all were significantly correlated with AET (R=-.48, -.42, -.52, respectively, all P<.01). The 3D-DHA and EGJ-CI also strongly correlated with each other (R=.84, P<.001). Both 3D-EGJ metrics were correlated with AET emphasizing the importance of both LES and CD function as a determinant of EGJ competence. 3D-DHA also strongly correlated with the EGJ-CI suggesting that EGJ-CI is strongly driven by the asymmetrical CD pressure component.

Symptom characteristics and esophageal motility of patients with different types of gastroesophageal junction

Objective To investigate the symptom, esophageal motility characteristics and the prevalence of gastroesophageal reflux disease (GERD) in patients with type Ⅰ, Ⅱ and Ⅲ gastroesophageal junction (EGJ) diagnosed by high resolution esophageal manometry (HREM). Methods From 6th January to 27th December in 2012, the clinical data of 171 patients with reflux symptoms and received HREM were retrospectively analyzed. According to the Chicago classification V. 3.0, the patients were divided into EGJ type Ⅰ, Ⅱ and Ⅲ groups. The age, body mass index (BMI), GERD related symptoms, esophageal motility parameters and the incidence of GERD were compared among the three groups. Chi-square test, t test and analysis of variance were used for statistical analysis. Relationship between EGJ types and other variables were analyzed by Spearman rank correlation. Results In 171 patients, 136 cases (79.5%) with type Ⅰ EGJ, 22 cases (12.9%) with type Ⅱ EGJ and 13 cases (7.6%) with type Ⅲ EGJ. The age of patients with type Ⅱ EGJ was significantly older than that of patients with type Ⅰ EGJ ((56.5±2.3) years vs (48.6±1.0) years, t=2.992, P=0.003), however the differences were not statisticant when compared with type Ⅲ EGJ patients ((51.2±3.8) years, P>0.05). The BMI of patients with type Ⅲ EGJ was higher than that of type Ⅰ and type Ⅱ EGJ patients ((26.0±1.3) kg/m2 vs (21.9±0.3) kg/m2 and (23.5±0.6) kg/m2), and the difference was statistically significant (t=4.082 and 2.108, both P<0.05). The resting pressure of lower esophageal sphincter (LES) of patients with type Ⅱ and Ⅲ EGJ were lower than that of type Ⅰ EGJ ((10.6±1.5) mmHg (1 mmHg=0.133 kPa) and (3.4±0.7) mmHg vs (17.1±0.7) mmHg), and the resting pressure of LES of type Ⅲ EGJ was lower than that of type Ⅱ EGJ ((3.4±0.7) mmHg vs (10.6±1.5) mmHg), and the differences were all statistically significant (t=-3.882, -6.411 and -2.769, all P<0.01). The amplitude of contraction at 11 cm above LES and distal contractile integral (DCI) of patients with type Ⅲ EGJ were both lower than those of patients with type Ⅰ EGJ ((32.2±5.4) mmHg vs (48.5±2.5) mmHg, and (392.0±94.1) mmHg·s·cm vs (805.1±61.4) mmHg·s·cm), and the differences were statistically significant (t=-2.580 and -2.041, both P<0.05). The incidences of GERD in patients with type Ⅰ, Ⅱ and Ⅲ EGJ were 68.4%(93/136), 77.3%(17/22) and 10/13, respectively, and the difference was not statistically significant (χ2 =1.021, P=0.600). EGJ types were positively correlated with age and BMI (r=0.214 and 0.290, both P<0.01). However, EGJ types were negatively correlated with the LES resting pressure, contraction amplitudes at 7 cm and 11 cm above the LES, and DCI (r=-0.474, -0.182, -0.333 and -0.191, all P<0.05). Conclusions Aging, overweight and obesity are risk factors of the LES and crural diaphragm separation. EGJ types are not predictable based on symptoms. The esophageal motility seems to decrease in patients with type Ⅱ and Ⅲ EGJ, the incidence of GERD in patients with type Ⅰ, Ⅱ and Ⅲ EGJ are all high. Key words: Gastroesophageal reflux; Gastroesophageal junction types; High resolution esophageal manometry

High resolution manometry and new classification of esophageal motility disorders.

To present application of Chicago classification criteria of esophageal motility disorders defined in high resolution manometry in clinical practice. High-resolution manometry is the most exact hi-tech diagnostic method for esophageal motor function disorders according to Chicago classification v3.0. Uniqueness of the method consists in capacity to define integrated quantitative and qualitative metrics of esophageal contractile function and to establish their specific disorders e.g.: change of intrabolus pressure at disorders of esophagogastric junction (EGj) outflow, hypercontractile esophagus, fragmented contractions and weak or failed peristalsis, distal esophageal spasm. Assessment of the type of achalasia subtypes has significant impact on the patients' treatment choice. According to anatomical location of the lower esophageal sphincter and crural diaphragm several morphological types of gastro-esophageal junction are defined that determine severity of gastroesophageal reflux disease. Multiple rapid swallow responses during esophageal high-resolution manometry reflect esophageal body peristaltic reserve and is a predictor of postoperative complications. Differential diagnosis of belching type became possible at combined application of high-resolution manometry and impedance measurement. High-resolution manometry is a fundamental diagnostic test of esophageal motor function disorders. Clinical application of this method significantly expands diagnostic potential and allows to carry out personalized treatment that increases treatment quality.

Relationship between the severity of reflux esophagitis and the esophageal motility features on high resolution manometry

Objective: To analyze esophageal motility dysfunction in gastroesophageal reflux disease (GERD) with different severity of esophagitis, and the relationship between the esophageal motility dysfunction and the severity of esophagitis. Methods: GERD patients simultaneously undergone endoscopy and high-resolution manometry were divided into four groups: Non-esophagitis (Non-erosive gastroesophageal reflux disease, NERD) group, mild esophagitis group, moderate esophagitis group and severe esophagitis group. The gender and age were matched for each group, and every group consisted of 80 cases. Nonparametric test was used to analyze the differences in HRM parameters, such as upper esophageal sphincter (UES) pressure, lower esophageal sphincter (LES) pressure, LES length, LES-CD (crural diaphragm) separation distance, and the percentage of failed peristalsis of the four groups, and the differences between each two of the groups were also analyzed. Results: Nonparametric test showed that the LES pressure and length decreased with the severity of esophagitis, and there were statistical differences (P<0.001, P=0.030). The failed peristalsis percentage increased with the severity of esophagitis and the difference was statistically significant (P<0.001). The LES-CD separation distance was increased with the severity of esophagitis and had statistically significance (P<0.001). When comparing the differences between each two of the groups, there were significant differences (P<0.001, P=0.012, P<0.001, P<0.001) between NERD group and severe esophagitis group in the HRM parameters of the lower esophageal sphincter pressure, the LES length, the LES-CD separation distance, and the percentage of ineffective swallowing in the NERD and severe esophagitis group. The detection rate of HH was significantly increased from NERD to severe esophagitis, the detection rate of HH was 6.3% to 82.5% in gastoracopy and 16.3% to 45.0% in HRM, and the diagnostic consistency was fair (Kappa Value: 0.31). Conclusions: Hypo-dynamic state of esophageal and HH are the main motility characteristics of erosive gastroesophageal reflux disease, Esophageal motility abnormalities increase in parallel with the severity of GERD from NERD to severe esophagitis, these motility disorders may also play important roles in causing esophagitis.

Three-Dimensional Myoarchitecture of the Lower Esophageal Sphincter and Esophageal Hiatus Using Optical Sectioning Microscopy

Studies to date have failed to reveal the anatomical counterpart of the lower esophageal sphincter (LES). We assessed the LES and esophageal hiatus morphology using a block containing the human LES and crural diaphragm, serially sectioned at 50 μm intervals and imaged at 8.2 μm/pixel resolution. A 3D reconstruction of the tissue block was reconstructed in which each of the 652 cross sectional images were also segmented to identify the boundaries of longitudinal (LM) and circular muscle (CM) layers. The CM fascicles on the ventral surface of LES are arranged in a helical/spiral fashion. On the other hand, the CM fascicles from the two sides cross midline on dorsal surface and continue as sling/oblique muscle on the stomach. Some of the LM fascicles of the esophagus leave the esophagus to enter into the crural diaphragm and the remainder terminate into the sling fibers of the stomach. The muscle fascicles of the right crus of diaphragm which form the esophageal hiatus are arranged like a “noose” around the esophagus. We propose that circumferential squeeze of the LES and crural diaphragm is generated by a unique myo-architectural design, each of which forms a “noose” around the esophagus.

Hiatus Hernia as a Cause of Dysphagia.

This review aims to discuss the putative relationship between hiatus hernia and dysphagia. Proposed mechanisms of dysphagia in patients with hiatus hernia are usually difficult to identify, but recent advances in technology (high-resolution manometry with or without concomitant impedance, ambulatory pH with impedance, videofluoroscopy, and the endoluminal functional lumen imaging probe (EndoFLIP)) and methodology (inclusion of swallows of various consistencies and volumes or shifting position during the manometry protocol) can help induce symptoms and identify the underlying disorder. Chronic reflux disease is often associated with hiatus hernia and is the most common underlying etiology. Dysmotility because of impaired contractility and vigor can occur as a consequence of repeated acid exposure from the acid pocket within the hernia, and the resultant poor clearance subsequently worsens this insult. As such, dysphagia appears to be more common with increasing hiatus hernia size. Furthermore, mucosal inflammation can lead to fibrotic stricture formation and in turn obstruction. On the other hand, there appears to be a difference in the pathophysiology of smaller sliding hernias, in that those with dysphagia are more likely to have extrinsic compression at the crural diaphragm as compared to those with reflux symptoms only. Sliding hiatus hernia, especially when small, does not commonly lead to dysmotility and dysphagia; however, in those patients with symptoms, the underlying etiology can be sought with new technologies and, in particular, the reproduction of normal eating and drinking during testing.

Functional morphology of the lower esophageal sphincter and crural diaphragm determined by three-dimensional high-resolution esophago-gastric junction pressure profile and CT imaging

The smooth muscles of the lower esophageal sphincter (LES) and skeletal muscles of the crural diaphragm (CD) provide a closure/antireflux barrier mechanism at the esophago-gastric junction (EGJ). A number of questions in regard to the pressure profile of the LES and CD remain unclear, e.g., 1) Why is the LES pressure profile circumferentially asymmetric, 2) Is the crural diaphragm (CD) contraction also circumferentially asymmetric, and 3) Where is the LES and CD pressure profile located in the anatomy of the esophagus and stomach? The three-dimensional (3-D) high-resolution esophageal manometry (HRM) catheter can record a detailed profile of the EGJ pressure; however, it does not allow the determination of the circumferential orientation of individual pressure transducers in vivo. We used computed tomography (CT) scan imaging in combination with 3-D EGJ pressure recordings to determine the functional morphology of the LES and CD and its relationship to the EGJ anatomy. A 3-D-HRM catheter with 96 transducers (12 rings, 7.5 mm apart, located over 9-cm length of the catheter, with eight transducers in each ring, 45° apart (Medtronics), was used to record the EGJ pressure in 10 healthy subjects. A 0.5-mm diameter metal ball (BB) was taped to the catheter, adjacent to transducer 1 of the catheter. The EGJ was recorded under the following conditions: 1) end-expiration (LES pressure) before swallow, after swallow, and after edrophonium hydrochloride; and 2) peak inspiration (crural diaphragm contraction) for tidal inspiration and forced maximal inspiration. A CT scan was performed to localize the circumferential orientation of the BB. The CT scan imaging allowed the determination of the circumferential orientation of the LES and CD pressure profiles. The LES pressure under the three end-expiration conditions were different; however, the shape of the pressure profile was unique with the LES length longer toward the lesser curvature of the stomach as compared with the greater curvature. The pressure profile revealed circular and axial pressure asymmetry, with greatest pressure and shortest cranio-caudal length on the left (close to the angle of His). The CD contraction with tidal and forced inspiration increases pressure in the cranial half of the LES pressure profile, and it was placed horizontally across the recording. The CD, esophagus, and stomach were outlined in the CT scan images to construct a 3-D anatomy of the region; it revealed that the hiatus (CD) is placed obliquely across the esophagus; however, because of the bend of the esophagus to the left at the upper edge of the hiatus, the two were placed at right angle to each other, which resulted in a horizontal pressure profile of the CD on the LES. Our observations suggest a unique shape of the LES, CD, and the anatomical relationship between the two, which provides a possible explanation as to why the LES pressure shows circumferential and axial asymmetry. Our findings have implication for the length and circumferential orientation of myotomy incision required for the ablation of LES pressure in achalasia esophagus.NEW & NOTEWORTHY We used computed tomography scan imaging with three-dimensional esophago-gastric junction (EGJ) pressure recordings to determine functional morphology of the lower esophageal sphincter (LES) and crural diaphragm and its relationship to EGJ anatomy. The LES pressure profile was unique with the LES length longer and pressures lower toward the lesser curvature of the stomach, as compared with the greater curvature. Our findings have implications for the length and circumferential orientation of myotomy incision required for the ablation of LES pressure in the achalasia esophagus.

Novel 3D high-resolution manometry metrics for quantifying esophagogastric junction contractility.

The esophagogastric junction (EGJ) is a complex sphincter composed of both the crural diaphragm (CD) and lower esophageal sphincter (LES). Three dimensional high-resolution manometry (3D-HRM) provides a dynamic 360° representation of EGJ pressure in which the CD has a distinct pressure signature. We aimed to develop 3D-HRM metrics to: (i) quantify the vigor of CD contractility, (ii) best eliminate the CD contribution and thereby isolate the LES component of EGJ contractility, and (iii) compare these metrics with conventional HRM metric of EGJ contractility. Twenty healthy subjects underwent 3D-HRM studies. Two novel 3D-HRM EGJ metrics, 3D-DHA , and 3D-LES pressure (3D-LESP) were devised and calculated to best approximate the CD and LES components of the composite EGJ pressure topography. These values were then compared to conventional HRM metrics of EGJ contractility, the EGJ contractile integral (EGJ-CI), inspiratory EGJ pressure and expiratory EGJ pressure. Mean 3D-DHA correlated most strongly with EGJ-CI (r=.82, P<.001), while the 3D-LESP correlated most strongly with inspiratory EGJ pressure (r=.91 P<.001) and expiratory EGJ pressure (r=.85, P<.001). We devised novel 3D-HRM metrics to quantify the CD (3D-DHA ) and LES (3D-LESP) elements of EGJ contractility. Both measures correlated strongly with conventional HRM metrics of EGJ contractility. The 3D-DHA , in particular, correlated strongly with the EGJ-CI suggesting that both are largely determined by CD contractility. It is hoped that future studies will show these new metrics useful in quantifying elements of the antireflux barrier in mechanistically defined subsets of gastro-esophageal reflux disease (GERD) patients.

Tu1290 - Swallow-Induced Transient Spatial Separation of Crural Diaphragm and Lower Esophageal Sphincter is Associated with Gastroesophageal Reflux

Tu1290 - Swallow-Induced Transient Spatial Separation of Crural Diaphragm and Lower Esophageal Sphincter is Associated with Gastroesophageal Reflux

Sa1681 - Functional and Anatomical Morphology of the Crural Diaphragm in Healthy Subjects Revealed by High Definition Les Pressure Profile and CT-Scan Imaging

Sa1681 - Functional and Anatomical Morphology of the Crural Diaphragm in Healthy Subjects Revealed by High Definition Les Pressure Profile and CT-Scan Imaging

Regional diaphragm volume displacement is heterogeneous in dogs.

Muscle shortening and volume displacement (VD) are critical determinants of the pressure-generating capacity of the diaphragm. The present study was designed to test the hypothesis that diaphragm VD is heterogeneous and that distribution of VD is dependent on regional muscle shortening, posture, and the level of muscle activation. Radioopaque markers were sutured along muscle bundles of the peritoneal surface of the crural, dorsal costal, midcostal, and ventral costal regions of the left hemidiaphragm in four dogs. The markers were followed by biplanar video fluoroscopy during quiet spontaneous breathing, passive inflation to total lung capacity (TLC), and inspiratory efforts against an occluded airway at three lung volumes spanning the vital capacity [functional residual capacity, functional residual capacity + ½ inspiratory capacity, and TLC in both the prone and supine postures]. Our data show the ventral costal diaphragm had the largest VD and contributed nearly two times to the total diaphragm VD compared with the dorsal costal portion. In addition, the ventral costal diaphragm contributed nearly half of the total VD in the prone position, whereas it only contributed a quarter of the total VD in the supine postition. During efforts against an occluded airway and during passive inflation to TLC in the supine position, the crural diaphragm displaced volume equivalent to that of the midcostal portion. Regional muscle shortening closely matched regional VD. We conclude that the primary force generator of the diaphragm is primarily dominated by the contribution of the ventral costal region to its VD.

Rumination syndrome: pathophysiology, diagnosis, and treatment.

Rumination syndrome is a functional gastrointestinal disorder characterized by effortless and repetitive regurgitation of recently ingested food from the stomach to the oral cavity followed by either re-swallowing or spitting. Rumination is thought to occur due to a reversal of the esophagogastric pressure gradient. This is achieved by a coordinated abdominothoracic maneuver consisting of a thoracic suction, crural diaphragm relaxation and an increase in intragastric pressure. Careful history is important in the diagnosis of rumination syndrome; patients often report "vomiting" or "reflux" and the diagnosis can therefore be missed. Objective testing is available with high resolution manometry or gastroduodenal manometry. Increase in intra-gastric pressure followed by regurgitation is the most important characteristic to distinguish rumination from other disorders such as gastroesophageal reflux. The mainstay of the treatment of rumination syndrome is behavioral therapy via diaphragmatic breathing in addition to patient education and reassurance. The purpose of this review was to critically appraise recent key developments in the pathophysiology, diagnosis and therapy for rumination syndrome. A literature search using OVID (Wolters Kluwer Health, New York, NY, USA) to examine the MEDLINE database its inception until May 2016 was performed using the search terms "rumination syndrome," "biofeedback therapy," and "regurgitation." References lists and personal libraries of the authors were used to identify supplemental information. Articles published in English were reviewed in full text. English abstracts were reviewed for all other languages. Priority was given to evidence obtained from randomized controlled trials when possible.

Esophagogastric Junction Morphology and Distal Esophageal Acid Exposure.

The Chicago classification has recently added a morphological subclassification for the esophagogastric junction (EGJ). Our aim was to assess the distal esophageal acid exposure in patients with this new Chicago EGJ-type IIIa and IIIb classification. From a prospectively collected high-resolution manometry (HRM) database, we identified patients who underwent 24-h pH study between October 2011 and June 2015 and were diagnosed with EGJ-type III based on HRM. Chicago EGJ-type III is defined as the inter-peak nadir pressure ≤gastric pressure and a lower esophageal sphincter (LES)-crural diaphragm (CD) separation >2cm [IIIa-pressure inversion point (PIP) remains at CD level and IIIb-PIP remains at LES level]. We classified the patients into reflux group [DeMeester score >14.72 or Fraction time pH (<4)>4.2%] and non-reflux group based on 24-h pH study. Fifty patients were identified that satisfied the study criteria, of which 37 patients (74%) were EGJ-type IIIa. In those with EGJ-type IIIb, abdominal LES length (AL) in reflux group was significantly shorter than the non-reflux group (0.8 vs. 1.8, p<0.05). EGJ-type IIIa patients showed significantly higher value for DeMeester score and Fraction time pH and more often had a positive pH study than EGJ-type IIIb patients (DeMeester score: 26.7 vs. 11.7, p<0.05; Fraction time pH: 7.9 vs. 2.6, p<0.05; positive pH study: 81.1 vs. 30.8%, p<0.001). Reflux was more common in LES-CD≥3cm than that in LES-CD<3cm (85 vs. 56.7%, p<0.05). A subset of patients with >2-cm LES-CD separation (type IIIb) maintain a physiological intra-abdominal location of the EGJ and are less likely to have reflux. A LES-CD≥3cm seems to discern a hiatus hernia of clinical significance.

How to Effectively Use High-Resolution Esophageal Manometry

How to Effectively Use High-Resolution Esophageal Manometry

Validation of criteria for the definition of transient lower esophageal sphincter relaxations using high‐resolution manometry

Criteria for transient lower esophageal sphincter relaxations (TLESRs) are well-defined for Dentsleeve manometry. As high-resolution manometry (HRM) is now the gold standard to assess esophageal motility, our aim was to propose a consensus definition of TLESRs using HRM. Postprandial esophageal HRM combined with impedance was performed in 10 patients with gastroesophageal reflux disease. Transient lower esophageal sphincter relaxations identification was performed by 17 experts using a Delphi process. Four investigators then characterized TLESR candidates that achieved 100% agreement (TLESR events) and those that achieved less than 25% agreement (non-events) after the third round. Logistic regression and decision tree analysis were used to define optimal diagnostic criteria. All diagnostic criteria were more frequently encountered in the 57 TLESR events than in the 52 non-events. Crural diaphragm (CD) inhibition and LES relaxation duration >10seconds had the highest predictive value to identify TLESR. Based on decision tree analysis, reflux on impedance, esophageal shortening, common cavity, upper esophageal sphincter relaxation without swallow and secondary peristalsis were alternate diagnostic criteria. Using HRM, TLESR might be defined as LES relaxation occurring in absence of swallowing, lasting more than 10seconds and associated with CD inhibition.

Normal and abnormal physiology, pharmacology, and anatomy of the gastroesophageal junction high-pressure zone.

The high-pressure zone of the gastroesophageal junction acts as a multifunctional valve that comprises different groups of smooth muscles located in the distal esophagus and the proximal stomach, in addition to the extrinsic crural diaphragm, composed of skeletal muscle. In this review article, we evaluate the current literature with respect to human subjects, discussing the anatomic locations and physiologic and pharmacologic processes controlling these muscles. These muscles work individually and as a group to prevent reflux of gastric contents while allowing anterograde passage of food and liquid and retrograde passage of gas. We also reviewed new findings with respect to abnormalities that are permissive of reflux of gastric contents into the esophagus, which may lead to gastroesophageal reflux disease.

Anatomical and functional deficiencies of the crural diaphragm in patients with esophagitis.

Inspiratory esophagogastric junction (EGJ) pressure is lower in gastroesophageal reflux disease (GERD) and patients fail to increase EGJ pressure during the inspiratory effort. The aim of this study was to assess the EGJ activity during inspiratory maneuvers (high-resolution manometry, HRM) and the crural diaphragm (CD) thickness (endoscopic ultrasound, EUS) in GERD. Twenty esophagitis patients (average age 45years, 7 grade A, 13 grade B) had HRM and EUS. Forty-three controls were recruited; 30 had HRM (average age 33years), and 13 had EUS (average age 40years). The EGJ contractility index (EGJ-CI) (mm Hg×cm) was measured during normal respiration and two inspiratory maneuvers: without and with inspiratory loads of 12, 24, and 48cmH2 O (TH-maneuvers). A composite metric for TH-maneuvers ("EGJ total activity") was defined as the product of the maximal EGJ pressure and the length of its aboral excursion during the maneuver (mm Hg×cm). The CD thickness (cm) was measured during expiration (12MHz). Expiratory lower esophageal sphincter pressure and integrated relaxation pressure were lower in GERD. The EGJ-CI and the "EGJ total activity" were lower in GERD during TH-maneuvers (48-cmH2 O load: 168.4±13.8 vs 114.8±9.6, P=.006). Patients failed to sustain the inspiratory CD activity across the 12 and 48-cmH2 O efforts. The CD was thinner in GERD patients (0.37±0.03 vs 0.49±0.04, P=.02). The CD thickness correlated with the increment in the "EGJ total activity" in GERD without a hiatal hernia (r=.702, P=.016, n=11). There are anatomical changes and functional failure of the CD in esophagitis patients supporting the possibility of a skeletal muscle deficiency in GERD.