Endoscopic pyloric suturing to facilitate weight loss: a canine model.

BACKGROUND: More than 66% of adults in United States are overweight or obese. OBJECTIVE: To decrease gastric emptying and cause early and prolonged satiety by endoscopically narrowing the gastric pylorus. DESIGN: Thirteen dogs were randomized into 3 groups (suture, sham, and control). SETTING: Animal facility. INTERVENTIONS: Sutures were placed across the pylorus in the 7 dogs in the suture group by using an endoscopic suturing device. Three sham dogs had endoscopy without suturing, and 3 control dogs did not have any intervention. MAIN OUTCOME MEASUREMENTS: Gastric emptying studies were conducted on all of the dogs by using 13C-octanoic acid breath tests. All dogs were monitored for daily food intake and weight gain/loss. RESULTS: The suture dogs decreased their food consumption by 48% (P < .02), whereas the sham and control dogs showed 9.5% increase (P = .16). The suture dogs lost 12.7% (P = .001) of their initial body weight, whereas the sham and control dogs gained 13.4% (P = .03). There was a delay in gastric emptying between the presuturing baseline and last postsuturing measurement by 30.75% (P = .005) in the suture dogs. In the sham plus control dogs, there was a delay in gastric emptying during the same period by only 6.75% (P = .55). LIMITATIONS: Long-term efficacy of the sutures was not evaluated. CONCLUSIONS: There was a significant weight loss and decreased food consumption along with a significant prolongation of gastric emptying in the suture dogs compared with the sham and control dogs.

Induced opening of the gastroesophageal junction occurs at a lower gastric pressure in gerd patients and in hiatal hernia subjects than in normal control subjects.

Purpose. To determine intragastric pressure threshold for inducing gastroesophageal junction (GEJ) opening in normal control subjects with and without hiatal hernia, and in patients with gastroesophageal reflux disease. Methods. This study was performed in 13 normal volunteers, 5 volunteers with hiatal hernia, and 3 patients with gastroesophageal reflux disease. During endoscopy a pressure transducer was used to measure baseline gastric pressures. The pressure in the stomach was measured while air was insufflated into the stomach until the gastroesophageal junction opened on endoscopic view. Results. There were two patterns of GEJ opening in normal volunteers. The mean opening pressure for Gastroesophageal junction in normal pattern-I, normal pattern-II, hiatal hernia, and Gastroesophageal reflux patients was 11.5, 12.6, 3.4, and 1.3 mmHg, respectively. Conclusions. GEJ opening is induced at a significantly lower pressure in subjects with hiatal hernia and in patients with gastroesophageal reflux disease than in normal volunteers.

Effect of atilmotin, a motilin receptor agonist, on esophageal, lower esophageal sphincter, and gastric pressures.

BACKGROUND: Motilin, an endogenous gastrointestinal (GI) hormone, increases upper gastrointestinal tract motility and is associated with phase III of the gastric migrating motor complex. The motilin receptor agonist, atilmotin, at doses of 6, 30 or 60 microg intravenously (IV), increases the early phase of gastric emptying. Prior studies at higher doses of 100-450 microg IV demonstrated that some subjects developed noncardiac chest pain. AIMS: The aim of this study is to determine the effects of atilmotin on esophageal, lower esophageal sphincter (LES), and gastric contractility and the development of esophageal-related symptoms. METHODS: Ten healthy volunteers underwent esophageal manometry to study the effects of atilmotin on upper GI motility. Five subjects were studied on three separate days following administration of saline placebo and subsequent IV bolus dose of atilmotin (6, 30 or 150 microg). Another five subjects were studied at the highest dose (150 microg). RESULTS: Atilmotin at 150 microg increased proximal gastric pressure by 6.5 mmHg (P = 0.001 compared with placebo). Atilmotin increased LES pressure at all studied doses; LES pressure increased from 24 +/- 2 mmHg following placebo injection to 34 +/- 4 mmHg following a 30 microg dose of atilmotin (P = 0.007). In the esophagus, atilmotin increased the percentage of failed swallows at the highest dose studied. Failed swallows increased from 17 +/- 7% following placebo injection to 36 +/- 7% following a 150 microg dose of atilmotin (P = 0.016). Atilmotin decreased distal esophageal contractile amplitude only at the highest dose studied, from 69 +/- 8 mmHg (placebo) to 50 +/- 5 mmHg following 150 microg atilmotin (P = 0.018). There were no serious adverse effects or episodes of chest pain with atilmotin. CONCLUSIONS: Atilmotin affects esophageal, LES, and gastric motility. LES and gastric pressures were increased, whereas there was disruption of esophageal peristalsis characterized by lower amplitude and failed contractions.

Minimally invasive measurement of esophageal variceal pressure and wall tension (with video).

BACKGROUND: There is no simple method to measure intravariceal pressure in patients with esophageal varices. OBJECTIVE: Our purpose was to develop a new noninvasive technique to measure resting intravariceal pressure and wall tension. DESIGN: A model was developed. A long balloon (varix) was fitted inside an airtight cylinder (esophagus). Fluid ran through the model varices to maintain 5 different constant pressures. An endoscope was placed in the model esophagus, and pressure was increased by air insufflation. The endoscopy and pressure readings from the esophagus and varix were recorded continuously until variceal collapse. SETTING: Patient studies were done in an endoscopy suite with the patient under fentanyl and midazolam sedation. PATIENTS: Esophageal pressure was measured during air insufflation in patients with varices until the varices collapsed. EUS was used to measure radius and wall thickness to calculate wall tension. RESULTS: In the varix model, the mean (SD) intraluminal esophageal pressures at variceal flattening for the model varices at 5, 10, 15, 20, and 25 mm Hg were 5.69 (0.34), 11 (0.32), 15.72 (0.51), 21.55 (0.63), and 25.8 (0.14) mm Hg. The correlation between actual and measured variceal pressure in the model at variceal flattening was r = 0.98. In the patients, a total of 10 varices in 3 patients were evaluated. The mean (SD) for the varices in each subject was 12.16 (2.4), 23.2 (1.3), and 6.5 (2.2) mm Hg for subjects 1, 2, and 3, respectively. CONCLUSION: Standard endoscopy with air insufflation and manometry can be used as an accurate, simple, and reproducible method to measure intravariceal pressure.

Tonic and phasic pyloric activity in response to CCK-octapeptide.

BACKGROUND: The purpose of this study was to determine whether a high-resolution solid-state catheter system could detect regional pressure changes within the antrum and pylorus in response to CCK-octapeptide. METHODS: Subjects received a 30 min infusion of CCK-octapeptide at either 0.02 or 0.06 microg kg(-1) h(-1). RESULTS: Five males and two females were studied. Mean antral pressure during phase I MMC increased from 5.3 +/- 2.1 to 9.9 +/- 2.4 mmHg (P = 0.028) after infusion. At the pylorus, only the 0.06 microg kg(-1) h(-1) dose increased tonic pressure (8.8 +/- 1.4 to 17.6 +/- 2.0 mmHg; P = 0.01) as compared with the 0.02 microg kg(-1) h(-1) dose (4.7 +/- 0.7 to 7.3 +/- 0.4 mmHg; P = NS). The peak pressure of pyloric phasic pressure waves was 153 +/- 28.4 mmHg and their frequency was 4.9 +/- 1.1 contractions min(-1). CONCLUSIONS: CCK-octapeptide elicits both tonic and phasic activity of the pyloric sphincter. The contractile response to a dose of 0.06 mug kg(-1) h(-1) is greater than the response to 0.02 mug kg(-1) h(-1).

Acoustic liver biopsy using endoscopic ultrasound.

BACKGROUND: Transabdominal ultrasound cannot be used to quantitate fibrosis in patients with cirrhosis because of variability in the abdominal wall thickness and variability in the components of the abdominal wall (fat versus muscle). Endoscopic ultrasound through the gastric wall is always at a constant distance, approximately 3 mm, away from the liver when the transducer is just below the gastroesophageal junction, thereby eliminating this variability. PURPOSE: To differentiate between cirrhotic and noncirrhotic liver using endoluminal ultrasound. METHODS: Eleven patients without known liver disease and eight patients with cirrhosis underwent endoscopic ultrasound using an Olympus linear ultrasound scope. The gain, contrast, frequency, and acoustic power were kept constant on the Aloka ultrasound processor. Videotaped images of the liver were recorded and then digitized on Image-Pro Plus software. The brightness of the image was adjusted to a standard brightness for each image and an area of interest was chosen using Photoshop 7.0. Vessels and artifacts were eliminated digitally and a histogram was produced using Photoshop to quantitate the pixel density for the area of interest from 0 (black) to 255 (white). Approximately 250,000 pixels were evaluated for each subject. The mean +/- standard deviation (SD) pixel density of the noncirrhotic subjects was evaluated against the cirrhotic patients using a Student unpaired t-test. RESULTS: The mean echogenecity in patients with cirrhosis was 116.85 and the mean echogenecity in patients without cirrhosis was 92.75 (P < 0.002). The mean standard deviation of the pixel density in patients with cirrhosis was 19.08 and the mean standard deviation of the pixel density in patients without cirrhosis was 13.25 (P < 0.0004). Using these criteria the subjects with cirrhosis were segregated from the noncirrhotic subjects (normal subjects and the subjects with steatosis) with 100% sensitivity and 100% specificity. CONCLUSION: A new method of evaluating the liver parenchyma (acoustic liver biopsy) that takes advantage of the proximity of the endoscopic ultrasound transducer to the liver and uses commercial image analysis technology that is inexpensive and widely available was developed. This is a preliminary study of this new technology, which demonstrates that endoscopic ultrasound, can be standardized in order to image, analyze, and compare the mean echogenecity and mean standard deviation of the pixel density in the liver in order to distinguish cirrhotic patients from patients without cirrhosis.

New observations on the gastroesophageal antireflux barrier.

The use of high-frequency ultrasound transducers combined with manometry in the gastrointestinal (GI) tract has yielded important findings concerning the anatomy, physiology, and pathophysiology of the high-pressure zone of the gastroesophageal junction and the sphincteric muscles within. These transducers have made previously invisible portions of the GI tract accessible to investigation. Three distinct high-pressure zones have been identified and correlated with anatomic structures: the extrinsic sphincter (crural diaphragm) and the two components of the intrinsic sphincter (an upper LES and a lower LES [the gastric sling fiber/clasp fiber complex]). This article discusses the possible underlying pathophysiology of gastroesophageal reflux disease; the biomechanics of the gastroesophageal junction high-pressure zone; and the mechanism of action of standard surgical and newer endoscopic therapies for gastroesophageal reflux disease.

Three-dimensional US volume analysis of gastric pseudotumors in a porcine model.

BACKGROUND: Tumor burden is difficult to estimate by endoscopy and conventional EUS. OBJECTIVE: The purpose of this study was to determine the accuracy and the reliability of a new 3-dimensional (3D) EUS system in a pseudotumor model (Olympus EUS EXERA EU-M60). DESIGN: A pseudotumor model was developed in a porcine stomach. Pseudotumors were created by injecting various volumes of US gel (0.3, 0.5, 0.7, and 1 mL) into porcine stomach specimens, and then the volume was measured in vitro. Two investigators made volume measurements by outlining the cross-sectional area of the pseudotumor at different radial planes. The instrument then automatically calculated the volume based on the outlined cross-sectional areas. The measured volume was compared with the actual volume of the pseudotumor by using a Bland-Altman analysis. Every second, third, fourth, fifth, sixth, and tenth image was measured to calculate the tumor volume and to determine the optimum number of images required for accurate volume determination. Inter- and intraobserver variability, percentage error, Bland-Altman analysis, analysis of variance (ANOVA), and kappa statistic were performed. SETTING: This study was performed in an in vitro animal model. PATIENTS: There were no patients involved in this study. MAIN OUTCOME MEASUREMENTS: Accuracy and reliability of pseudotumor volume measurement. RESULTS: When averaging across all measurements, the overall average mean error was 3.25%. The overall inter-rater reliability as measured by intraclass correlation coefficient was 0.78. The overall intra-rater reliability as measured by intraclass correlation coefficient was 0.99. Bland-Altman analysis and ANOVA showed similar low variability for measured volumes based on image frequencies for volume calculations between every other and every sixth image but greater variability for measured volumes based on every tenth image. Larger pseudotumors were measured with a slight decrease in mean percentage error. The kappa statistic for interobserver variability was .61, which demonstrated substantial agreement among observers. LIMITATIONS: The major limitation of this technology is the penetration of the US beam to evaluate large tumors, because the US transducer is high frequency (20 MHz) and, therefore, has a limited penetration. CONCLUSIONS: In conclusion, the new Olympus EUS EXERA EU-M60 3D US probe allowed for accurate volume measurements of small pseudotumors in porcine stomach model in vitro. There was substantial evaluator agreement, with a low interobserver variability. Larger pseudotumors were measured with a slightly lower percentage error than smaller pseudotumors. Volumes measured with a greater number of radial images were measured slightly more accurately. We plan to test this device in patients with GI tumors in the near future.

Use of endoluminal ultrasound to evaluate gastrointestinal motility.

The use of high-frequency ultrasound transducers in the gastrointestinal tract (GI) has already yielded remarkable findings concerning the anatomy, physiology and pathophysiology of the GI tract and of various motility disorders. These transducers have made completely invisible portions of the GI tract (the longitudinal smooth muscle, muscles of the upper esophageal sphincter, components of the gastroesophageal junction high-pressure zone, and the muscle of the anal sphincter complex) accessible to investigation. Use of simultaneous ultrasound and manometry has allowed the exploration of the normal physiology of peristaltic contraction. The components of the high-pressure zone of the distal and proximal esophagus have been isolated and the movement of these components has been studied individually and as a group. Various esophageal motility disorders have been investigated including achalasia, scleroderma, Barrett's esophagus and diffuse esophageal spasm. The possible etiology of the symptoms of esophageal chest pain and heartburn (sustained esophageal contractions of the longitudinal smooth muscle), have been studied. The possible underlying pathophysiology of GERD (the missing gastric clasp and sling fiber pressure profile) has been explored. Three-dimensional high-frequency ultrasound imaging has allowed the peristaltic contraction sequence to be viewed in a completely new and unique manner. The biomechanics of both esophageal contraction and the gastroesophageal junction high-pressure zone have been investigated and the mechanical advantage of esophageal shorting has been studied. The mechanism of action of standard surgical and newer endoscopic therapies for GERD has been defined. Future applications of this technology are limited only by our imagination.

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.