Enhancing the diagnostic yield of esophageal manometry using distension-contraction plots of peristalsis and artificial intelligence.

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.

Impaired sliding between the lower esophageal sphincter and crural diaphragm (esophageal hiatus) in patients with achalasia esophagus.

Swallow-related axial shortening of the esophagus results in the formation of phrenic ampulla in normal subjects; whether it is the case in achalasia esophagus is not known. The goal is to study axial shortening of the esophagus and relative movement between the lower esophageal sphincter (LES) and crural diaphragm (CD) in normal subjects and patients with achalasia. A novel method, isoimpedance contour excursion at the lower edger of LES, as a marker of axial esophageal shortening was validated using X-ray fluoroscopy (n = 5) and used to study axial shortening and separation between the LES and CD during peristalsis in normal subjects (n = 15) and patients with achalasia type 2 esophagus (n = 15). Abdominal CT scan images were used to determine the nature of tissue in the esophageal hiatus of control (n = 15) and achalasia patients (n = 15). Swallow-induced peristalsis resulted in an axial excursion of isoimpedance contours, which was quantitatively similar to the metal clip anchored to the LES on X-ray fluoroscopy (2.3 ± 1.4 vs. 2.1 ± 1.4 cm with deep inspiration and 2.7 ± 0.6 cm vs. 2.7 ± 0.6 cm with swallow-induced peristalsis). Esophageal axial shortening with swallows in patients with achalasia was significantly smaller than normal (1.64 ± 0.5 cm vs. 3.59 ± 0.4 cm, P < 0.001). Gray-level matrix analysis of CT images suggests more "fibrous" and less fat in the hiatus of patients with achalasia. Lack of sliding between the LES and CD explains the low prevalence of hiatus hernia, and low compliance of the LES in achalasia esophagus, which likely plays a role in the pathogenesis of achalasia.NEW & NOTEWORTHY Swallow-related axial shortening of the esophagus is reduced, and there is no separation between the lower esophageal sphincter and crural diaphragm (CD) with swallowing in patients with achalasia esophagus. Fat in the hiatal opening of the esophagus appears to be replaced with fibrous tissue in patients with achalasia, resulting in tight anchoring between the LES and CD. The above findings explain low prevalence of hiatus hernia and the low compliance of the LES in achalasia esophagus.

Esophageal wall compliance/stiffness during peristalsis in patients with functional dysphagia and high-amplitude esophageal contractions.

Recent studies that utilized distension/contraction plots to study peristalsis reveal poor distension of the esophagus in patients with functional dysphagia and high-amplitude contractions [high-amplitude esophageal contractions (HAECs)] even though the contraction phase of peristalsis is normal in these patients. Our goal was to determine biomechanical properties of the esophageal wall and bolus flow characteristics in patients with functional dysphagia and HAEC during primary peristalsis. Studies were performed on 30 healthy subjects, 30 patients with functional dysphagia, and 25 patients with HAEC. Subjects swallowed 10 mL, 0.5 N saline bolus in the Trendelenburg position to study primary peristalsis. A custom-built software (Dplots) determined peak distension from the impedance measurements, pressure at peak distension, wall tension (pressure × radius), wall distensibility [cross-sectional area (CSA)/pressure], and bolus flow (cm3/s) in four segments of esophagus (between upper and lower esophageal sphincter). Luminal CSA of distal esophagus was smaller, and average bolus flow rate was faster in patients with functional dysphagia and HAEC. Esophageal wall distensibility, a measure of esophageal wall compliance was lower and wall tension was higher in the distal esophagus of both patient groups compared with normal subjects. Ultrasound imaging confirmed poor distension of the esophagus. A trend toward greater wall thickness at the peak of distension was found in patients with functional dysphagia compared with normal subjects. A stiffer or noncompliant esophageal wall is the reason for poor distension of the esophagus during primary peristalsis in patients with functional dysphagia and HAEC.NEW & NOTEWORTHY We studied healthy asymptomatic subject, patients with functional dysphagia (FD), and patients with high-amplitude esophageal contractions (HAEC). Our data show that in patients with HAEC and functional dysphagia, luminal distension is smaller (low luminal CSA at peak distension), intraluminal pressure is higher, and liquid bolus travels faster through the esophagus as compared with normal subjects. We conclude that patients with functional dysphagia and HAEC have a stiffer distal esophageal wall during bolus transport related to primary peristalsis.

Distension contraction plots of pharyngeal/esophageal peristalsis: next frontier in the assessment of esophageal motor function.

Esophageal peristalsis consists of initial inhibition (relaxation) followed by excitation (contraction), both of which move sequentially in the aboral direction. Initial inhibition results in receptive relaxation and bolus-induced luminal distension, which allows propulsion by the contraction with minimal resistance to flow. Similar to the contraction wave, luminal distension has unique waveform characteristics in normal subjects; both are modulated by bolus volume, bolus viscosity, and posture, suggesting a possible cause-and-effect relationship between the two. Distension contraction plots in patients with dysphagia with normal bolus clearance [high-amplitude esophageal contractions (HAECs), esophagogastric junction outflow obstruction (EGJOO), and functional dysphagia (FD)] reveal two major findings: 1) unlike normal subjects, there is luminal occlusion distal to bolus during peristalsis in certain patients, i.e., with type 3 achalasia and nonobstructive dysphagia; and 2) bolus travels through a narrow lumen esophagus during peristalsis in patients with HAECs, EGJOO, and FD. Aforementioned findings indicate a relative dynamic obstruction to the bolus flow during peristalsis and reduced distensibility of esophageal wall in the bolus segment of the esophagus. We speculate that a normal or supernormal contraction wave pushing bolus against resistance is the mechanism of dysphagia sensation in significant number of patients. Representations of distension and contraction, combined with objective measures of flow timing and distensibility are complementary to the current scheme of classifying esophageal motility disorders based solely on the characteristics of contraction phase of peristalsis. Better understanding of the distensibility of the bolus-containing segment of the esophagus during peristalsis will lead to the development of novel medical and surgical therapies in the treatment of dysphagia in significant number of patients.

Three-Dimensional Pressure Profile of the Lower Esophageal Sphincter and Crural Diaphragm in Patients with Achalasia Esophagus.

BACKGROUND & AIMS: Smooth 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. METHODS: We 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. RESULTS: The 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.

Botox injection into the lower esophageal sphincter induces hiatal paralysis and gastroesophageal reflux.

BACKGROUND: Endoscopic intrasphincteric injection of Botox (ISIB) is used routinely for the treatment of achalasia esophagus and other spastic motor disorders. Studies show that the ISIB reduces the smooth muscle lower esophageal sphincter (LES) pressure. The esophageal hiatus, formed by the right crus of diaphragm, surrounds the cranial half of the LES and works like an external LES. We studied the effects of ISIB on the LES and hiatal contraction and gastroesophageal reflux (GER). Fourteen patients treated with ISIB were studied. Esophageal manometry-impedance recordings were performed before and after the ISIB. Hiatal contraction was assessed during tidal inspiration, forced inspiration, Müller's maneuver, and straight leg raise. In 6 subjects, the manometry were repeated 6-12 mo after the ISIB. The esophagogastric junction (EGJ) pressure was measured at end expiration (LES pressure) and at the peak of maneuvers (hiatal contraction). Transdiaphragmatic pressure (pdi; force of diaphragmatic contraction) was measured at the peak of forced inspiration. GER was measured from the impedance recordings. The EGJ pressure at end expiration (LES pressure) decreased significantly after the Botox injection. The peak EGJ pressure at tidal inspiration, forced inspiration, Müller's maneuver, and straight leg raise was also dramatically reduced by the ISIB. There was no effect of Botox on the pdi during forced inspiration. Seven of 10 subjects demonstrated GER during maneuvers following the ISIB. Six to 12 mo after ISIB, the LES and hiatal contraction pressure returned to the pre-ISIB levels. ISIB, in addition to decreasing LES pressure, paralyzes the esophageal hiatus (crural diaphragm) and induces GER.NEW & NOTEWORTHY The sphincter mechanism at the lower end of the esophagus comprises smooth muscle lower esophageal sphincter (LES) and skeletal muscle crural diaphragm (hiatus). Current thinking is that the endoscopic intrasphincteric injection of Botox (ISIB), used routinely for the treatment of achalasia esophagus, reduces LES pressure. Our study shows that ISIB, even though injected into the LES, diffuses into the hiatus and causes its paralysis. These findings emphasize the importance of esophageal hiatus as an important component of the antireflux barrier and that the ISIB is refluxogenic.

Relationship between distension-contraction waveforms during esophageal peristalsis: effect of bolus volume, viscosity, and posture.

High-resolution esophageal manometry (HRM) in its current form assesses only the contraction phase of peristalsis. Degree of esophageal distension ahead of contraction is a surrogate of relaxation and can be measured from intraluminal esophageal impedance measurements. The characteristics of esophageal contractions, i.e., their amplitude, duration, velocity, and modulating factors, have been well studied. We studied the effect of bolus volume and viscosity and posture on swallow-induced distension and contraction and the temporal relationship between the two. HRM impedance recordings of 50 healthy subjects with no esophageal symptoms were analyzed. Eight to ten swallows of 5 and 10 mL of 0.5 N saline and a viscous bolus were recorded in the supine and Trendelenburg positions. Custom-built computer software generated the distension-contraction plots and numerical data of the amplitudes of distension (cross-sectional area) and contraction, and the temporal relationship between distension and peak contraction. The hallmarks of distension waveforms are that 1) distension peak, similarly to contraction, travels the esophagus in a peristaltic fashion, and the amplitude of distension increases from the proximal-to-distal direction; 2) the amplitude of distension is greater with 10 mL than with 5 mL and greater in Trendelenburg than in supine posture; and 3) bolus viscosity increases the amplitude of distension and alters the temporal relationship between distension and contraction waveforms. We describe the characteristics of esophageal distension during peristalsis and the relationship between distension and contraction in a relatively large cohort of normal subjects. These data can be used to compare differences between normal subjects and patients with various esophageal motility disorders in future studies.NEW & NOTEWORTHY We studied esophageal distension (surrogate of inhibition) ahead of contraction during peristalsis from intraluminal esophageal impedance measurements. Esophageal distension, similarly to contraction, travels the esophagus in a sequential manner, and the amplitude of esophageal distension increases from proximal to distal direction in the esophagus. Bolus volume, viscosity and posture have significant effects on the amplitude of distension and its temporal relationship with contraction.

Loop analysis of the anal sphincter complex in fecal incontinent patients using functional luminal imaging probe.

Cardiac loops have been used extensively to study myocardial function. With changes in cardiac pump function, loops are shifted to the right or left. Functional luminal imaging probe (FLIP) recordings allow for loop analysis of the anal sphincter and puborectalis muscle (PRM) function. The goal was to characterize anal sphincter area-pressure/tension loop changes in fecal incontinence (FI) patients. Fourteen healthy subjects and 14 patients with FI were studied. A custom-designed FLIP was placed in the vagina and then in the anal canal, and deflated in 20-ml steps, from 90 to 30 ml. At each volume, subjects performed maximal voluntary squeezes. Area-pressure (AP) and area-tension (AT) loops were generated for each squeeze cycle. Three-dimensional ultrasound imaging of the anal sphincter and PRM were obtained to determine the relationship between anal sphincter muscle damage and loop movements. With the increase in bag volume, AP loops and AT loops shifted to the right and upward in normal subjects (both anal and vaginal). The shift to the right was greater, and the upward movement was less in FI patients. The difference in the location of AP loops and AT loops was statistically significant at volumes of 50 ml to 90 ml (P < 0.05). A similar pattern was found in the vaginal loops. There is a significant relationship between the damage to the anal sphincter and PRM, and loop location of FI patients. We propose AP and AT loops as novel ways to assess the anal sphincter and PRM function. Such loops can be generated by real-time measurement of pressure and area within the anal canal.NEW & NOTEWORTHY We describe the use of area-pressure (AP) and area-tension (AT)-loop analysis of the anal sphincters and puborectalis muscles in normal subjects and fecal incontinent patients using the functional luminal imaging probe (FLIP). There are differences in the magnitude of the displacement of the loops with increase in the FLIP bag volume between normal subjects and patients with fecal incontinence. The latter group shifts more to the right in AP and AT space.

Topographical plots of esophageal distension and contraction: effects of posture on esophageal peristalsis and bolus transport.

Each swallow induces a wave of inhibition followed by contraction in the esophagus. Unlike contraction, which can easily be measured in humans using high-resolution manometry (HRM), inhibition is difficult to measure. Luminal distension is a surrogate of the esophageal inhibition. The aim of this study was to determine the effect of posture on the temporal and quantitative relationship between distension and contraction along the entire length of the esophagus in normal healthy subjects by using concurrent HRM, HRM impedance (HRMZ), and intraluminal ultrasound (US). Studies were conducted in 15 normal healthy subjects in the supine and Trendelenburg positions. Both manual and automated methods were used to extract quantitative pressure and impedance-derived features from the HRMZ recordings. Topographical plots of distension and contraction were visualized along the entire length of the esophagus. Distension was also measured from the US images during 10-ml swallows at 5 cm above the lower esophageal sphincter. Each swallow was associated with luminal distension followed by contraction, both of which traversed the esophagus in a sequential/peristaltic fashion. Luminal distension (US) and esophageal contraction amplitude were greater in the Trendelenburg compared with the supine position. Length of esophageal breaks (in the transition zone) were reduced in the Trendelenburg position. Change in posture altered the temporal relationship between distension and contraction, and bolus traveled closer to the esophageal contraction in the Trendelenburg position. Topographical contraction-distension plots derived from HRMZ recordings is a novel way to visualize esophageal peristalsis. Future studies should investigate if abnormalities of esophageal distension are the cause of functional dysphagia. NEW & NOTEWORTHY Ascending contraction and descending inhibition are two important components of peristalsis. High-resolution manometry only measures the contraction phase of peristalsis. We measured esophageal distension from intraluminal impedance recordings and developed novel contraction-distension topographical plots to prove that similar to contraction, distension also travels in a peristaltic fashion. Change in posture from the supine to the Trendelenburg position also increased the amplitude of esophageal distension and contraction and altered the temporal relationship between distension and contraction.

Genesis of Esophageal Pressurization and Bolus Flow Patterns in Patients With Achalasia Esophagus.

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.

Measuring length-tension function of the anal sphincters and puborectalis muscle using the functional luminal imaging probe.

The functional luminal imaging probe (FLIP) has been used to measure the distensibility of the anal canal. We hypothesized that with increasing distension of the anal canal with FLIP there will be an increase in length of the anal sphincter muscle allowing measurement of the length-tension function of anal sphincter and puborectalis muscles (PRM). We studied 14 healthy nulliparous women. A custom-designed FLIP bag (30-mm diameter) was placed in the vagina and then in the anal canal, distended in 10-ml steps with volumes ranging from 30 to 90 ml. At each volume, subject performed maximal voluntary squeezes. Length-tension measurements were also made with a manometric probe system. Tension was calculated (pressure × radius) in Newtons per meter using a custom software program. Peak tensions at different FLIP volumes were compared with the manometric data. No change in the luminal CSA was noted at low fluid volumes; the sphincter muscles were able to fully collapse the FLIP bag within the anal canal/vagina even at rest. At larger volumes, with each squeeze there was an increase in the bag pressure and reduction in the cross-sectional area, which represents concentric contraction of the muscle. Both rest and squeeze tension increased with the increase in volume in the anal as well as vaginal canal indicating that the external anal sphincter and puborectalis muscles produce more tension when lengthened. FLIP device, which has been used to describe the distensibility of the anal canal can also provide information on the length-tension function of the anal sphincters and PRM. NEW & NOTEWORTHY The functional luminal imaging probe (FLIP) has been used to describe the distensibility of the anal canal. This report is the first to describe the use of the FLIP in the vaginal canal and the anal canal to provide information on the length-tension function of the anal sphincter and puborectalis muscles, which may provide clinicians with additional information regarding the active components of muscle contraction involved in the anal closure function.

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.

A Predictive Model to Identify Patients With Fecal Incontinence Based on High-Definition Anorectal Manometry.

BACKGROUND & AIMS: Three-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). METHODS: In 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. RESULTS: The 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). CONCLUSIONS: We developed and validated a novel prediction model to analyze 3D-HDAM data. This system can accurately distinguish patients with FI from control subjects.

Why so Many Patients With Dysphagia Have Normal Esophageal Function Testing.

Esophageal peristalsis involves a sequential process of initial inhibition (relaxation) and excitation (contraction), both occurring from the cranial to caudal direction. The bolus induces luminal distension during initial inhibition (receptive relaxation) that facilitates smooth propulsion by contraction travelling behind the bolus. Luminal distension during peristalsis in normal subjects exhibits unique characteristics that are influenced by bolus volume, bolus viscosity, and posture, suggesting a potential interaction between distension and contraction. Examining distension-contraction plots in dysphagia patients with normal bolus clearance, ie, high-amplitude esophageal peristaltic contractions, esophagogastric junction outflow obstruction, and functional dysphagia, reveal 2 important findings. Firstly, patients with type 3 achalasia and nonobstructive dysphagia show luminal occlusion distal to the bolus during peristalsis. Secondly, patients with high-amplitude esophageal peristaltic contractions, esophagogastric junction outflow obstruction, and functional dysphagia exhibit a narrow esophageal lumen through which the bolus travels during peristalsis. These findings indicate a relative dynamic obstruction to bolus flow and reduced distensibility of the esophageal wall in patients with several primary esophageal motility disorders. We speculate that the dysphagia sensation experienced by many patients may result from a normal or supernormal contraction wave pushing the bolus against resistance. Integrating representations of distension and contraction, along with objective assessments of flow timing and distensibility, complements the current classification of esophageal motility disorders that are based on the contraction characteristics only. A deeper understanding of the distensibility of the bolus-containing esophageal segment during peristalsis holds promise for the development of innovative medical and surgical therapies to effectively address dysphagia in a substantial number of patients.

Selective dysfunction of the crural diaphragm in patients with chronic restrictive and obstructive lung disease.

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.

Fecal incontinence patients categorized based on anal pressure and electromyography: Anal sphincter damage and clinical symptoms.

BACKGROUND: Disruption of external anal sphincter muscle (EAS) is an important factor in the multifactorial etiology of fecal incontinence (FI). OBJECTIVES: We categorize FI patients into four groups based on the location of lesion in neuromuscular circuitry of EAS to determine if there are differences with regards to fecal incontinence symptoms severity (FISI) score, age, BMI, obstetrical history, and anal sphincter muscle damage. METHODS: Female patients (151) without any neurological symptoms, who had undergone high-resolution manometry, anal sphincter EMG, and 3D ultrasound imaging of the anal sphincter were assessed. Patients were categorized into four groups: Group 1 (normal)-normal cough EMG (>10 µV), normal squeeze EMG (>10 µV), and normal anal squeeze pressure (>124 mmHg); Group 2 (cortical apraxia, i.e., poor cortical activation)-normal cough EMG, low squeeze EMG, and low anal squeeze pressure; Group 3 (muscle damage)-normal cough EMG, normal squeeze EMG, and low anal squeeze pressure; and Group 4 (pudendal nerve damage)-low cough EMG, low squeeze EMG, and low anal squeeze pressure. RESULTS: The four patient groups were not different with regards to the patient's age, BMI, parity, and FISI scores. 3D ultrasound images of the anal sphincter complex revealed significant damage to the internal anal sphincter, external anal sphincter, and puborectalis muscles in all four groups. CONCLUSION: The FI patients are a heterogeneous group; majority of these patients have significant damage to the muscles of the anal sphincter complex. Whether biofeedback therapy response is different among different patient groups requires study.

Esophageal Symptoms and Lumbosacral Back Pain.

BACKGROUND AND AIMS: Esophageal symptoms, that is, heartburn, regurgitation, dysphagia, and chest pain are common in the general population. Also common are symptoms of back pain related to pathology in the lumbosacral spine. The right crus of the diaphragm that forms the esophageal hiatus, originates from lumbar spine, may be affected by lumbar spine pathology resulting in esophageal symptoms. We studied whether there was an association between esophageal symptoms and spine symptoms. METHODS: Two patient groups of 150 each were investigated: group 1 (ES); patients referred to the esophageal manometry study for assessment of esophageal symptoms, group 2 (SC); patients undergoing screening colonoscopy (control group). Both groups completed standardized questionnaires assessing esophageal and spine symptoms. RESULTS: Back pain was reported by 74% of patients in the ES group as compared to 55% of patients in the SC group. Thirty percent of patients in the SC group reported one or more esophageal symptoms and these patients were regrouped with the ES group, resulting in 2 groups, ES1 and SC1, with and without esophageal symptoms, respectively. The ES1 group was 3.3 times more likely to experience back pain compared to the SC1 group (95% confidence interval: 1.95-5.46). Thoracolumbar was the most common site of pain in both groups. Pain score was greater for the group with esophageal symptoms compared to controls. Narcotic intake for most patients in the ES1 group was for back pain. CONCLUSION: A strong association between esophageal symptoms and thoracolumbar back pain raises the possibility that structural and functional changes in the esophageal hiatus muscles related to thoracolumbar spine pathology lead to esophageal dysmotility and symptoms.

Bolus flow and biomechanical properties of the esophageal wall during primary esophageal peristalsis: Effects of bolus viscosity and posture.

BACKGROUND: Studies show that intraluminal impedance recordings of the esophagus allow one to measure the luminal distension during peristalsis, an important parameter for calculation of the biomechanical properties of esophageal wall. The goal was to determine the effect of subject posture and bolus viscosity on the biomechanical properties of esophageal wall, and the rate of bolus flow along the length of the esophagus during primary peristalsis. METHODS: High-resolution manometry impedance recordings were obtained in 14 normal healthy subjects. Swallows of 10 ml saline and viscous bolus were recorded in the supine and Trendelenburg positions. User identified the region of interest, and a custom-designed software extracted parameters of interest such as bolus flow rate, esophageal wall tension, and esophageal wall distensibility in four equal segments of the esophagus. KEY RESULTS: Bolus flow rate decreases along the length of the esophagus, being slowest in the distal esophagus. Bolus flow rate is smaller in the Trendelenburg position and with viscous bolus as compared with supine position and saline bolus. Esophageal wall tension is greater in the Trendelenburg position and with viscous bolus as compared with the supine position and saline bolus. The esophageal wall distensibility is larger in the distal as compared with proximal esophagus, which is true for both the saline and viscous bolus. CONCLUSIONS & INFERENCES: We report, for the first time, bolus flow rate and biomechanical properties of the esophageal wall during swallow-induced primary peristalsis. Future studies may investigate biomechanical basis of esophageal motility disorders using the methodology described.

Rhythmic contraction but arrhythmic distension of esophageal peristaltic reflex in patients with dysphagia.

BACKGROUND: Reason for dysphagia in a significant number of patients remains unclear even after a thorough workup. Each swallow induces esophageal distension followed by contraction of the esophagus, both of which move sequentially along the esophagus. Manometry technique and current system of classifying esophageal motility disorders (Chicago Classification) is based on the analysis of the contraction phase of peristalsis. GOAL: Whether patients with unexplained dysphagia have abnormalities in the distension phase of esophageal peristalsis is not known. METHODS: Using Multiple Intraluminal esophageal impedance recordings, which allow determination of the luminal cross-sectional area during peristalsis, we studied patients with nutcracker esophagus (NC), esophagogastric junction outflow obstruction (EGJOO), and functional dysphagia (FD). RESULTS: Distension contraction plots revealed that swallowed bolus travels significantly faster through the esophagus in all patient groups as compared to normals. The luminal cross-sectional area (amplitude of distension), and the area under the curve of distension were significantly smaller in patients with NC, EGJOO, and FD as compared to normals. Bolus traverses the esophagus in the shape of an "American Football" in normal subjects. On the other hand, in patients the bolus flow was fragmented. ROC curves revealed that bolus flow abnormalities during peristalsis are a sensitive and specific marker of dysphagia. CONCLUSION: Our findings reveal abnormality in the distension phase of peristalsis (a narrow lumen esophagus) in patients with dysphagia. We propose that the esophageal contraction forcing the swallowed bolus through a narrow lumen esophagus is the cause of dysphagia sensation in patients with normal contraction phase of peristalsis.