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Background & aimsSmooth muscles of the lower esophageal sphincter (LES) and skeletal muscle of the crural diaphragm (esophagus hiatus) provide the sphincter mechanisms at the esophagogastric junction (EGJ). We investigated differences in the 3-dimensional (3D) pressure profile of the LES and hiatal contraction between healthy subjects and patients with achalasia esophagus.MethodsWe performed a prospective study of 10 healthy subjects (controls; 7 male; mean age, 60 ± 15 years; mean body mass index, 25 ± 2) and 12 patients with a diagnosis of achalasia (7 male; mean age, 63 ± 13 years; mean body mass index, 26 ± 1), enrolled at a gastroenterology clinic. Participants underwent 3D high-resolution manometry (3DHRM) with a catheter equipped with 96 transducers (for the EGJ pressure recording). A 0.5-mm metal ball was taped close to the transducer number 1 of the 3DHRM catheter. EGJ pressure was recorded at end-expiration (LES pressure) and at the peak of forced inspiration (hiatal contraction). Computed tomography (CT) scans were performed to localize the circumferential location of the metal ball on the catheter. Esophagus, LES, stomach, right and left crus of the diaphragm, and spine were segmented in each CT scan slice images to construct the 3D morphology of the region.ResultsThe metal ball was located at the 7 o'clock position in all controls. The circumferential orientation of metal ball was displaced 45 to 90 degrees in patients with achalasia compared with controls. The 3D-pressure profile of the EGJ at end-expiration and forced inspiration revealed marked differences between the groups. The LES turns to the left as it entered from the chest into the abdomen, forming an angle between the spine and LES. The spine-LES angle was smaller in patients with achalasia (104°) compared with controls (124°). Five of the 10 subjects with achalasia had physical breaks in the left crus of the diaphragm CONCLUSIONS: Besides LES, the 3D pressure profile of the EGJ can indicate anatomic and functional abnormalities of the crural diaphragm muscle in patients with achalasia esophagus. Further studies are needed to define the nature of hiatal and crural diaphragm dysfunction in patients with achalasia of the esophagus.

Background/aimsThe esophageal hiatus is formed by the right crus of the diaphragm in the majority of subjects. Contraction of the hiatus exerts a sphincter-like action on the lower esophageal sphincter (LES). The aim is to study the hiatal anatomy (using CT scan imaging) and function (using high-resolution manometry [HRM]), and esophageal motor function in patients with sliding and paraesophageal hiatal hernia.MethodsWe assessed normal subjects (n = 20), patients with sliding type 1 hernia (n = 18), paraesophageal type 2 hernia (n = 19), and mixed type 3 hernia (n = 19). Hernia diagnosis was confirmed on the upper gastrointestinal series. The hiatal morphology was constructed from the CT scan images. The LES pressure and relaxation, percent peristalsis, bolus pressure, and hiatal squeeze pressure were assessed by HRM.ResultsThe CT images revealed that the esophageal hiatus is formed by the right crus of the diaphragm in all normal subjects and 86% of hernia patients. The hiatus is elliptical in shape with a surface area of 1037 mm2 in normal subjects. The hiatal dimensions were larger in patients compared to normal subjects. The HRM revealed impaired LES relaxation and higher bolus pressure in patients with paraesophageal compared to the sliding hernia. The hiatal pinch on HRM was recognized in significantly higher number of patients with sliding as compared to paraesophageal hernia.ConclusionsUsing a novel approach, we provide details of the esophageal hiatus in patients with various kinds of hiatal hernia. Impaired LES relaxation in paraesophageal hernia may play a role in its pathophysiology and genesis of symptoms.

BackgroundThis manuscript summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance, terminology used, and interpretation of anorectal function testing including anorectal manometry (focused on high-resolution manometry), the rectal sensory test, and the balloon expulsion test. Based on these measurements, a classification system for disorders of anorectal function is proposed.MethodsTwenty-nine working group members (clinicians/academics in the field of gastroenterology, coloproctology, and gastrointestinal physiology) were invited to six face-to-face and three remote meetings to derive consensus between 2014 and 2018.Key recommendationsThe IAPWG protocol for the performance of anorectal function testing recommends a standardized sequence of maneuvers to test rectoanal reflexes, anal tone and contractility, rectoanal coordination, and rectal sensation. Major findings not seen in healthy controls defined by the classification are as follows: rectoanal areflexia, anal hypotension and hypocontractility, rectal hyposensitivity, and hypersensitivity. Minor and inconclusive findings that can be present in health and require additional information prior to diagnosis include anal hypertension and dyssynergia.Conclusions and inferencesThis framework introduces the IAPWG protocol and the London classification for disorders of anorectal function based on objective physiological measurement. The use of a common language to describe results of diagnostic tests, standard operating procedures, and a consensus classification system is designed to bring much-needed standardization to these techniques.

IntroductionThe current "gold standard" to diagnose anal sphincter morphology and disruptions utilizes low-frequency (3-9 MHz) ultrasound (US) imaging techniques that provide a general outline of the sphincter muscles, but not their microstructural details. High-frequency US transducers (7-15 MHz) have been used to study the muscle architecture (direction of muscle fascicles) in the limb muscle.AimsThe goal of our study was to visualize the microstructural anatomy of the anal sphincters, specifically the external anal sphincter (EAS), using high-frequency US imaging.MethodsStudies were conducted in asymptomatic female and male subjects and patients with fecal incontinence. US images were acquired using a low-frequency US (3-9 MHz) and high-frequency (7-15 MHz) US transducer. The latter was placed intra-anally to image the anal canal at 12, 9, 3, and 6 o'clock positions.ResultsThe low-frequency US images revealed the general outline of the anal sphincter muscles. On the other hand, high-frequency imaging visualized muscle fascicles and connective tissue inside the external anal sphincter (EAS). In FI patients, there was loss of muscle fascicles and alteration in the echo-intensity pattern in the region of damaged EAS suggestive of muscle fibrosis.ConclusionHigh-frequency ultrasound imaging is a powerful tool to visualize the microstructural details of the EAS. Our studies show that damage to the EAS muscle results in the alteration of its myoarchitecture, that is, loss of muscle fascicles and increase in the muscle connective tissue.

Despite the importance of pelvic floor muscles, significant controversy still exists about the true structural details of these muscles. We provide an objective analysis of the architecture and orientation of the superficial muscles of the perineum using a novel approach. Magnetic Resonance Diffusion Tensor Images (MR-DTI) were acquired in 10 healthy asymptomatic nulliparous women, and 4 healthy males. Global tractography was then used to generate the architecture of the muscles. Micro-CT imaging of a male cadaver was performed for validation of the fiber tracking results. Results show that muscles fibers of the external anal sphincter, from the right and left side, cross midline in the region of the perineal body to continue as transverse perinea and bulbospongiosus muscles of the opposite side. The morphology of the external anal sphincter resembles that of the number '8' or a "purse string". The crossing of muscle fascicles in the perineal body was supported by micro-CT imaging in the male subject. The superficial muscles of the perineum, and external anal sphincter are frequently damaged during child birth related injuries to the pelvic floor; we propose the use of MR-DTI based global tractography as a non-invasive imaging technique to assess damage to these muscles.

BackgroundHow much anal sphincter dysfunction contributes to fecal incontinence (FI) is not clear. High-definition anorectal manometry (HDAM) and functional luminal imaging probe (Endoflip) are two new techniques to study anal sphincter function.AimsThe goal was to compare the diagnostic utility of HDAM and Endoflip using optimal feature(s) in each modality for FI diagnosis.MethodsBlinded classification was carried out on 70 female subjects (32 FI & 38 controls), using 3 prominent machine-learning clustering techniques, with 3 distance metrics. For HDAM, descriptive statistics, shape, and textural features characterizing the spatial relationship of pixels in the HDAM high-pressure zone, and for Endoflip, permutations of pressure and CSA combinations (ie, multiplication, division, or individually) at rest and squeeze were tested.ResultsIntramodality: (a) Endoflip: Best clustering was obtained using the combination of the ratio of CSA over pressure at 40 and 50 mL at rest, which had significantly better specificity (P  0.05). Optimal Endoflip feature set differed significantly in specificity compared to HDAM maximal pressure at both rest (P

BACKGROUND & AIMS:In patients with achalasia esophagus, swallows induce simultaneous pressure waves known as esophageal pressurization. We studied the mechanism of esophageal pressurization and bolus flow patterns in patients with type 2 or type 3 achalasia. METHODS:We recorded high-resolution manometry with impedance and intraluminal ultrasound images concurrently in patients with type 2 achalasia (n = 6) or type 3 achalasia (n = 8) and in 10 healthy subjects (controls) during swallows of 5 mL of 0.5N saline. For each swallow, the ultrasound image was aligned with the pressure and impedance tracings to determine cavity and contact pressure, bolus arrival, bolus dwell time, and changes in muscle thickness at 5 cm and 10 cm above the lower esophageal sphincter. RESULTS:In patients with type 2 achalasia, esophageal pressurization was associated with an increase in the muscle thickness and luminal narrowing but not complete luminal closure (ie, cavity pressure). Bolus arrival time in the distal esophagus after the onset of a swallow was delayed in patients with type 3 achalasia compared with control individuals because of early luminal closure. The early luminal closure was associated with a decrease in the muscle thickness. The bolus dwell time was shorter in patients with type 3 achalasia compared with control individuals. In patients with type 3 achalasia, the onset of simultaneous pressure wave was always a cavity pressure, but during contraction there were different periods of cavity and contact pressures in association with increases in muscle thickness that resulted in bolus segmentation. CONCLUSIONS:We observed distinct mechanisms of esophageal pressurization and bolus flow patterns in patients with type 2 or type 3 achalasia esophagus compared with control individuals. These findings will increase our understanding of the mechanisms of dysphagia.

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.

Background/Aims Pharyngeal pump, esophageal peristalsis, and phrenic ampulla emptying play important roles in the propulsion of bolus from the mouth to the stomach. There is limited information available on the mechanism of normal and abnormal phrenic ampulla emptying. The goal of our study is to describe the relationship between bolus flow and esophageal pressure profiles during the phrenic ampulla emptying in normal subjects and patient with phrenic ampulla dysfunction. Methods Pressure (using topography) and bolus flow (using changes in impedance) relationship through the esophagus and phrenic ampulla were determined in 15 normal subjects and 15 patients with retrograde escape of bolus from the phrenic ampulla into esophagus during primary peristalsis. Results During the phrenic ampulla phase, 2 high pressure peaks (proximal, related to lower esophageal sphincter and distal, related to crural diaphragm) were observed in normal subjects and patients during the phrenic ampulla emptying phase. The proximal was always higher than the distal one in normal subjects; in contrast, reverse was the case in patients with the retrograde escape of bolus from the phrenic ampulla into the esophagus. Conclusions We propose that a strong after-contraction of the lower esophageal sphincter plays an important role in the normal phrenic ampullary emptying. A defective lower esophageal after-contraction, along with high crural diaphragm pressure are responsible for the phrenic ampulla emptying dysfunction. [ABSTRACT FROM AUTHOR]

Our prior study reveals that the distension-contraction profiles using high-resolution manometry impedance recordings can distinguish patients with dysphagia symptom but normal esophageal function testing ("functional dysphagia") from control subjects. The aim of this study was to determine the diagnostic value of the recording protocol used in our prior studies (10-mL swallows with subjects in the Trendelenburg position) against the standard clinical protocol (5-mL swallows with subjects in the supine position). We used advanced machine learning techniques and robust metrics for classification purposes. Studies were performed on 30 healthy subjects and 30 patients with functional dysphagia. A custom-built software was used to extract the relevant distension-contraction features of esophageal peristalsis. Ensemble methods, i.e., gradient boost, support vector machines (SVMs), and logit boost, were used as the primary machine learning algorithms. Although the individual contraction features were marginally different between the two groups, the distension features of peristalsis were significantly different. The receiver operating characteristic (ROC) curve values for the standard recording protocol and the distension features ranged from 0.74 to 0.82; they were significantly better for the protocol used in our prior studies, ranging from 0.81 to 0.91. The ROC curve values using three machine learning algorithms were far superior for the distension than the contraction features of esophageal peristalsis, revealing a value of 0.95 for the SVM algorithm. Current patient classification for esophageal motility disorders, based on the contraction phase of peristalsis, ignores a large number of patients who have an abnormality in the distension phase of peristalsis. Distension-contraction plots should be the standard for assessing esophageal peristalsis in clinical practice. NEW & NOTEWORTHY: Our findings underscore the superiority of distension features over contraction metrics in diagnosing esophageal dysfunctions. By leveraging state-of-the-art machine learning techniques, our study highlights the diagnostic potential of distension-contraction plots of peristalsis. Implementation of these plots could significantly enhance the accuracy of identifying patients with esophageal motor disorders, advocating for their adoption as the standard in clinical practice. [ABSTRACT FROM AUTHOR]

Wnt-β catenin is an important signaling pathway in the genesis of fibrosis in many organ systems. Our goal was to examine the role of Wnt pathway in the external anal sphincter (EAS) injury-related fibrosis and muscle dysfunction. New Zealand White female rabbits were subjected to surgical EAS myotomy and administered local injections of either a Wnt antagonist (sFRP-2; daily for 7 days) or saline. Anal canal pressure and EAS length-tension (L-T) were measured for 15 weeks after which the animals were sacrificed. Anal canal was harvested and processed for histochemical studies (Masson trichrome stain), molecular markers of fibrosis (collagen and transforming growth factor-β) and immunostaining for β catenin. Surgical myotomy of the EAS resulted in significant impairment in anal canal pressure and EAS muscle L-T function. Following myotomy, the EAS muscle was replaced with fibrous tissue. Immunostaining revealed β catenin activation and molecular studies revealed 1.5-2 fold increase in the levels of markers of fibrosis. Local injection of sFRP-2 attenuated the β catenin activation and fibrosis. EAS muscle content and function was significantly improved following sFRP-2 treatment. Our studies suggest that upregulation of Wnt signaling is an important molecular mechanism of injury related EAS muscle fibrosis and sphincter dysfunction.

Background & aimsThree-dimensional high-definition anorectal manometry (3D-HDAM) is used to assess anal sphincter function; it determines profiles of regional pressure distribution along the length and circumference of the anal canal. There is no consensus, however, on the best way to analyze data from 3D-HDAM to distinguish healthy individuals from persons with sphincter dysfunction. We developed a computer analysis system to analyze 3D-HDAM data and to aid in the diagnosis and assessment of patients with fecal incontinence (FI).MethodsIn a prospective study, we performed 3D-HDAM analysis of 24 asymptomatic healthy subjects (control subjects; all women; mean age, 39 ± 10 years) and 24 patients with symptoms of FI (all women; mean age, 58 ± 13 years). Patients completed a standardized questionnaire (FI severity index) to score the severity of FI symptoms. We developed and evaluated a robust prediction model to distinguish patients with FI from control subjects using linear discriminant, quadratic discriminant, and logistic regression analyses. In addition to collecting pressure information from the HDAM data, we assessed regional features based on shape characteristics and the anal sphincter pressure symmetry index.ResultsThe combination of pressure values, anal sphincter area, and reflective symmetry values was identified in patients with FI versus control subjects with an area under the curve value of 1.0. In logistic regression analyses using different predictors, the model identified patients with FI with an area under the curve value of 0.96 (interquartile range, 0.22). In discriminant analysis, results were classified with a minimum error of 0.02, calculated using 10-fold cross-validation; different combinations of predictors produced median classification errors of 0.16 in linear discriminant analysis (interquartile range, 0.25) and 0.08 in quadratic discriminant analysis (interquartile range, 0.25).ConclusionsWe developed and validated a novel prediction model to analyze 3D-HDAM data. This system can accurately distinguish patients with FI from control subjects.

Background: Gastroesophageal reflux (GER) is known to be associated with chronic lung diseases. The driving force of GER is the transdiaphragmatic pressure (Pdi) generated mainly by costal and crural diaphragm contraction. The latter also enhances the esophagogastric junction (EGJ) pressure to guard against GER. Methods: The relationship between Pdi and EGJ pressure was determined using high resolution esophageal manometry in patients with interstitial lung disease (ILD, n = 26), obstructive lung disease (OLD, n‐ = 24), and healthy subjects (n = 20). Key Results: The patient groups did not differ with respect to age, gender, BMI, and pulmonary rehabilitation history. Patients with ILD had significantly higher Pdi but lower EGJ pressures as compared to controls and OLD patients (p < 0.001). In control subjects, the increase in EGJ pressure at all‐time points during inspiration was greater than Pdi. In contrast, the EGJ pressure during inspiration was less than Pdi in 14 patients with ILD and 7 patients with OLD. The drop in EGJ pressure was usually seen after the peak Pdi in ILD group (p < 0.0001) and before the peak Pdi in OLD group, (p = 0.08). Nine patients in the ILD group had sliding hiatus hernia, compared to none in control subjects (p = 0.003) and two patients in the OLD, (p = 0.04). Conclusions and Inferences: A higher Pdi and low EGJ pressure, and dissociation between Pdi and EGJ pressure temporal relationship suggests selective dysfunction of the crural diaphragm in patients with chronic lung diseases and may explain the higher prevalence of GERD in ILD as seen in previous studies. [ABSTRACT FROM AUTHOR]