Vinod K. Thangada

Comparison of a Salivary/Sputum Pepsin Assay with 24-Hour Esophageal pH Monitoring for Detection of Gastric Reflux into the Proximal Esophagus, Oropharynx, and Lung

The purpose of this study was to determine whether measurement of salivary/sputum pepsin could be used as a surrogate marker for detecting gastroesophageal reflux using 24-hr esophageal pH monitoring as the gold standard. Patients with gastroesophageal reflux symptoms underwent simultaneous 24-hr esophageal pH monitoring and collection of saliva and sputum samples for pepsin measurement using a recently developed assay. In all, 16 patients provided 19 positive (10.6%) and 161 negative pepsin assays. The mean pH values for the positive pepsin samples were lower then the negative samples at both the proximal [5.34 (95% CI, 4.94–5.75) vs 6.12 (95% CI, 6.03–6.20; P <0.01)] and distal [4.97 (95% CI, 4.61–5.33) vs 6.03 (95% CI, 5.92–6.15; P < 0.01)] pH probes. Proximal esophageal reflux was not detected in patients who had a negative pepsin assay (N = 12); in contrast, proximal esophageal reflux was documented in three of four patients with a positive assay. In conclusion, detection of pepsin in the saliva and/or sputum may provide a noninvasive method to test for the proximal reflux of gastric contents.

Muscle shortening along the normal esophagus during swallowing.

Longitudinal shortening of the esophagus during peristaltic contraction has been previously analyzed globally using spaced mucosal clips. This method gives a relatively crude measurement. In this study, local longitudinal shortening (LLS) was evaluated using simultaneous high-resolution endoluminal ultrasound (HREUS) and manometry based on basic principles of muscle mechanics. We sought to determine if there are regional differences in LLS of the esophageal muscle during swallow-induced peristaltic contraction and evaluate shortening of the circular smooth muscle (CSM) and longitudinal smooth muscle (LSM) of the esophagus.Twenty normal subjects underwent simultaneous HREUS/manometry at 4 levels (5, 10, 15, and 20 cm above the upper border of the lower esophageal sphincter [LES] high-pressure zone) in the esophagus with 5-mL swallows of water. Ultrasound images were recorded with synchronized manometric pressure data. The images were digitized and the cross-sectional surface area (CSA) of the LSM, CSM, and total muscle (TM) were measured at baseline (at rest) and at peak intraluminal pressure (implying peak CSM contraction) during swallowing. LLS was calculated for the CSM and LSM using the principle of mass conservation, whereby the change in CSA relative to the resting CSA is quantitatively equal to the relative change in length of a local longitudinal muscle segment.CSM, LSM, and TM all shortened longitudinally, with the circular muscle shortening more than the longitudinal muscle, LLS of the CSM and TM layers at 5 cm above the LES was significantly greater than at 20 cm (CSM: 30% difference, P < .001; TM: 18% difference, P < .05). The greater shortening of LSM at 5 versus 20 cm was found not to be statistically significant (11% difference, P > .05). Peak intraluminal pressure strongly correlated with peak muscle thickness of all layers at all levels (r = 0.96–0.98).LLS increases from the proximal to the distal esophagus during bolus transport. CSM and LSM both shorten longitudinally, with CSM shortening more than LSM. The increase in LLS increases the efficiency of peristaltic contraction and likely contributes to the axial displacement of the LES preceding hiatal opening and esophageal emptying.

Evaluation of the Upper Esophageal Sphincter (UES) Using Simultaneous High-Resolution Endoluminal Sonography (HRES) and Manometry

The aim of this study was to characterize the motion, morphology, and pressure of the upper esophageal sphincter (UES). The UES and its surrounding structures were evaluated in seven normal subjects and four human cadavers, using simultaneous high-resolution endoluminal sonography and manometry. The UES musculature on ultrasound is a C-shaped structure with an angle of 107 ± 19°. The mean peak resting UES pressure was 74 mm Hg, with a total cross-sectional area (CSA) of 0.87 ± 0.33 cm2. During swallowing, the UES moved in an orad direction. Localizing the UES sonographically, the peak UES pressure in the cadavers was 19.7 ± 10.0 mm Hg. The UES has a greater muscular CSA and resting pressure than the upper esophageal body. In the cadaver studies, the UES was imaged in conjunction with a significant increase in pressure, indicating that the pressure is due to passive mechanical conformational changes.

A new ultrasound-guided esophageal variceal pressure-measuring device.

OBJECTIVE:To develop a noninvasive method and device to determine intravariceal pressure and variceal wall tension by measuring the variables of the Laplace equation and test this device in a model of esophageal varices.METHODS:Two variceal pressure measurement devices were constructed. The first device consists of an Olympus 20 MHz ultrasound transducer placed next to a latex balloon catheter attached to a pressure transducer. The second device was constructed by placing the same ultrasound transducer inside a latex condom balloon attached to a pressure transducer. These pressure measurement devices were tested blindly in varix models with different intravariceal pressures, by inflating the balloon to flatten the varix models. Each variceal pressure was measured 10 times by two separate investigators blinded to the actual pressures. The mean intravariceal pressures were calculated. The variceal models were made of a latex balloon filled with water and coffeemate.RESULTS:The correlation coefficient between the actual and measured varix pressures for both devices was 0.99. The percent error ranged from 0 to 10%. The correlation coefficient between the investigators making the blinded measurements for both devices was 0.98.CONCLUSION:Two pressure-measuring devices were developed to determine intravariceal pressure in a model varix system. These devices demonstrate a low percent error and a high correlation to the actual variceal pressures with low intra- and interobserver variability. These devices have the potential to measure all the variables of the Laplace equation for wall tension. We plan to test these devices in human subjects.

Volume (3-dimensional) space-time reconstruction of esophageal peristaltic contraction by using simultaneous US and manometry

BACKGROUND Conventional 3-dimensional endoluminal US was modified to evaluate peristaltic contractions in the esophagus. METHODS Two-dimensional US images and simultaneous intraluminal pressures were acquired during peristaltic contractions by locating the transducer at fixed positions in the esophagus in 6 normal volunteers during swallowing. Three-dimensional images were reconstructed by using a computer-based 3-dimensional algorithm with time as the x axis. RESULTS The peristaltic contraction sequence was viewed as a 3-dimensional US image. The geometric configuration of the esophagus, the muscle thickness, and corresponding pressures were evaluated. The 3-dimensional images demonstrate 4 phases of the peristaltic contraction sequence. CONCLUSIONS Three-dimensional time-resolved reconstruction of endoluminal US images of the esophagus and simultaneous recording of manometric data allow visualization of geometric changes and correlation with pressure changes during peristaltic contraction. Four phases of the peristaltic contraction sequence are demonstrated clearly on the 3-dimensional space-time images.

Three-dimension time resolved reconstruction of esophageal peristaltic contractions using simultaneous ultrasound (US) and manometry

Background: Endohiminal ultrasound (US) images of the esophagus can be reconstructed in 3D space by moving the US transducer at a constant velocity along the esophagus, and then stacking the images using computer reconstruction algorithms. This technique was modified to evaluate peristaltic contractions in the esophagus by using a stationary probe and moving the esophagus around the probe (peristaltic contraction). Time was used as a variable (x-axis). Purpose: To evaluate peristaltic contractions in the normal esophagus using 3D time resolved reconstruction of endoluminal US images and simultaneous manometry. Method: 2D US images and simultaneous intraluminal pressure of peristaltic contractions were acquired by keeping a 20MHz high-frequency endoluminal US transducer/manometry probe at a fixed position in the esophagus of 6 normal vohimeers during swallowing. 3D time resolved US images were reconstructed using a computer-based 3D algorithm with time as the x-axis. Result: The peristaltic contraction sequence can be viewed as a 3D US image with the X-axis representing time and Y and Z axes representing space on the ultrasound images (see figure). The geometric configuration of the esophagus, the muscle thickness of the circular smooth muscle, longitudinal smooth muscle, total muscle and corresponding pressure can be evaluated during the peristaltic contraction. Conclusion: 3D time resolved reconstruction of endoluminal US images and simultaneous pressure data allow the visualization of geometric changes and correlation of muscle thickness with pressure changes during the peristalttc contraction sequence. Funded through an NIH grant R01 DK59500-01. units, a.u.), mammal relative enhancement, time of arrival of contrast inflow, time-to-peak (T-peak), wash-in (W-in), wash-out (W-out), and brevity-of-enhancement (time between points of W-in and W-out rate) (BrevEnh). Results: 5emiqnantitative data were obtained for all subjects. Comparing perfusion parameters for the pancreatic head between V vs. CPpatients showed highly significant differences for T-peak (15,4 _+ 6,1 vs 46,6 16,6 sec), W-in (99,6 39,5 vs 58,8 -+ 13,3 a.u./sec), and for BrevEnh (21,5 _+ 12,3 vs 53,3 -15,8 sec), whereas no differences were found for the other parameters measured. Discussion: MRI perfusion parameters most representative for CP were T-peak, W-in, and BrevEnFi. This is compatible with the hypothesis of an increased resistance to the normal parenchymal perfusion due to tissue ischemia. A limitation is that all patients had moderate to severe CP. The significant differences of perfusion parameters in CP vs; normal volunteers is not yet proven in mild forms of CP. Additional studies in patients with upper abdominal pain suggestive of CP, are being performed.