Lower Esophageal Sphincter In Patients Research Articles

Functional Importance of Laparoscopic Sleeve Gastrectomy for the Lower Esophageal Sphincter in Patients with Morbid Obesity

Obesity is characterized by excess body fat measured in body mass index (BMI), which is the weight in kilograms (kg) divided by the height in square meters [m(2)]. In the Northern Hemisphere, the prevalence of overweight has increased by up to 34%. This situation is associated with high incidence of comorbidities such as gastroesophageal reflux disease. Bariatric surgery is the only effective treatment for severe obesity, resulting in amelioration of obesity comorbidities. Data on LES competence following sleeve gastrectomy (SG), one of the several bariatric procedures, are conflicting. In a prospective study, we enrolled 37 patients and divided them into two subgroups in order to evaluate lower esophageal sphincter pressure (LESP) and esophageal motility before and after laparoscopic sleeve gastrectomy (LSG) by means of stationary esophageal manometry. A study collective also underwent a gastroscopy. Participants (20) were healthy controls who volunteered. Preoperative median BMI in group I (control) differed statistically significantly (p < 0.0001) as compared to groups II and III (22 vs. 50.5 or 47.5kg/m², respectively). After LSG, the BMI of groups II and III decreased to 39.5 and 45kg/m², respectively. Postoperatively, LESP increased significantly, namely, from preoperative 8.4 to 21.2mmHg in group II and from 11 to 24mmHg (p < 0.0001) in group III. Tubular esophageal motility profits from LSG. As expected, the gastroscopy findings ranged from cardiac insufficiency, esophagitis and hiatal hernia to gastric ulcer. LSG significantly increased lower esophageal pressure independent of weight loss after LSG and may protect obese patients from gastroesophageal reflux.

PWE-083 Relationship between BMI and the function of the lower oesophageal sphincter in patients with normal upper gastrointestinal endoscopy

Introduction Western populations have recently experienced a substantial rise in both obesity and gastro-oesophageal reflux disease (GORD). There is growing evidence of a link between both conditions with higher BMI associated with greater prevalence of GORD symptoms, Barrett9s oesophagus and oesophageal adenocarcinoma. Currently, the most common dyspeptic patients seen in clinical practice are H pylori negative with a normal endoscopy. It is unclear if BMI has any effect on oesophageal physiology in these patients. Aims To examine the association between BMI and the function of the lower oesophageal sphincter (LOS) in dyspeptic patients with a normal endoscopy. Methods Patients with dyspepsia, a normal endoscopy and negative for H pylori had their BMI measured followed by assessment with water perfused oesophageal manometry and 24-h oesophageal pH monitoring. The LOS pressure, LOS length and LOS intra-abdominal length (high pressure zone distal to respiratory inversion point) were measured by station pull through. This involved withdrawing the catheter at 1 cm increments every minute with the patients sitting. Pressures were expressed using intragastric pressure as baseline. 24-h oesophageal acid exposure was measured as the per cent time pH Results 105 patients (46 males) were studied (mean age 44 years range 20–74). The median BMI was 26 (range 17.6–40.4) with 39% overweight and 20% obese. Higher BMI was associated with higher oesophageal per cent time pH Conclusion In patients with normal endoscopy there is a strong association between BMI and impaired function of the gastro-oesophageal barrier. The mechanism of this association requires to be investigated.

Functional analysis of long-term outcome after Heller's myotomy for achalasia

Treatment of achalasia aims at reducing the pressure of the lower esophageal sphincter (LES) and palliate symptoms. Our objective in this study was to investigate functional changes of the esophagus after Heller myotomy and evaluate their influence on postoperative gastroesophageal reflux and esophageal morphologic changes. Between 1980 and 2003, 216 patients with achalasia underwent Heller myotomy, associated with anterior partial fundoplication (Dor fundoplication). Preoperative and long-term outcome data were collected from these patients at our hospital. The objective was to analyze esophageal functional results after Heller myotomy in the long term. Results were classified as excellent, good, fair, or poor, according to Vantrappen and Hellemans' modified classification. One-year, 2-year, 5-year, 10-year, and 20-year postoperative follow-up information was available in 100% of all patients, 91.7%, 85.1%, 60%, 52.6%, and 45.9%, respectively. There were no perioperative deaths. One year after the surgery, all patients had a significant reduction in symptoms of dysphagia and regurgitation. Five years, 10 years, 15 years, and 20 years after surgery, there were 77.2% of patients (142 in 184), 68.1%, 57.1%, and 54.5%, respectively, who were satisfied (excellent to good) with surgery. No esophageal peristalsis was demonstrated in patients during follow-up. Contractile waves in the body of the esophagus were simultaneous. The difference in the distal esophageal amplitude, the LES relaxation rate, and LES pressures in the anterior wall and/ or two sides was significant (P < 0.05) when compared before and after operation. However, there was no significant difference in the LES length and LES pressure in the posterior side. The change of direction of the LES pressure and the relaxation of LES correlate with long-term outcomes. Postoperative gastroesophageal reflux rates, including nocturnal reflux, increased with time. The percentage of patients whose esophageal diameter became normal or remained mildly increased with time in the first 10 years after surgery changed significantly. Myotomy is an effective way to palliate symptoms in patients with achalasia. Adequate myotomy can lead to reduction of LES pressure in two or three directions, which may facilitate esophageal emptying by gravity. Surgical intervention does not lead to the return of esophageal peristalsis. Functional damage of LES in patients with achalasia is irreversible.

Lower esophageal sphincter analysis using computerized manometry in patients with chagasic megaesophagus

Due to the introduction of computer technology into manometry laboratories, three-dimensional manometric images of the lower esophageal sphincter can be constructed based on radially oriented pressures, a method termed 'computerized axial manometry.' Calculation of the sphincter pressure vector volume using this method is superior to standard manometric techniques in assessing lower esophageal sphincter function in patients with gastroesophageal reflux disease and idiopathic achalasia. Despite similarities between idiopathic achalasia and chagasic esophagopathy found using clinical, radiological, and manometric studies, controversy around lower esophageal sphincter pressure persists. The goal of this study was to analyze esophageal motor disorders in Chagas' megaesophagus using computerized axial manometry. Twenty patients with chagasic megaesophagus (5 men, 15 women, and average age 50.1 years, range 17-64) were prospectively studied. For three-dimensional imaging construction of the lower esophageal sphincter, a low-complacency perfusion system and an eight-channel manometry probe with four radial channels placed in the same level were used. For probe traction, the continuous pull-through technique was used. Results showed that the lower esophageal sphincter of patients with chagasic megaesophagus have significantly elevated pressure, length, asymmetry, and vector volumes compared to those of normal volunteers (P < 0.05). Aperistalsis of the esophageal body waves was observed in all patients and contraction amplitude was lower than that in normal patients. We conclude that patients with chagasic megaesophagus have hypertonic lower esophageal sphincter and aperistalsis of the esophageal body.

ASGE Technology Status Evaluation Report: wireless esophageal pH monitoring system

ASGE Technology Status Evaluation Report: wireless esophageal pH monitoring system

Oral Presentations : Tme

With the introduction of computational technology in esophageal physiology laboratories, tridimensional imaging of the lower esophageal sphincter (LES) started to be performed based on calculations of the radial pressure of each segment, a method named computerized axial manometry. This technology allows the calculation of the LES vector volume, better than conventional manometry when evaluating changes in that sphincter in patients with gastroesophageal reflux disease and idiopathic achalasia. Despite the similarities between idiopathic achalasia and chagasic esophagopathy, proved by clinical, radiological and manometric studies, some controversies around LES pressure still remain. The aim of this study was to analyze the LES in the chagasic megaesophagus using computerized axial manometry. Twenty patients with chagasic megaesophagus (5 men and 15 women, from 17 to 64 years old: average 50.15 years) were prospectively studied. For tridimensional imaging of the lower esophageal sphincter, a low complacency perfusion system and an eight channels manometry probe, with four radial channels placed in the same level, were used. For probe traction, the continuous removal technique was used. Results from chagasic megaesophagus patients were compared to the normal individuals. Results showed that the lower esophageal sphincter of patients with chagasic megaesophagus have significantly elevated pressure, length, asymmetry and vector volumes than those from comparing group (P < 0.05). Results from this study lead to the conclusion that patients with chagasic megaesophagus have lower esophageal sphincter hypertony.

Effects of sildenafil on lower esophageal sphincter in patients with hypertensive LES

Effects of sildenafil on lower esophageal sphincter in patients with hypertensive LES

Long-term results and prognostic factors in the treatment of achalasia with botulinum toxin.

Endoscopic therapy of achalasia by injection of botulinum toxin into the lower esophageal sphincter has very limited adverse effects and is initially successful in 70 % of patients. However, this result only lasts for 6 - 9 months on average in most patients and only half of them benefit for more than 1 year. The aim of this study was to find out which factors are predictive for a good long-term success. We retrospectively studied 25 patients with achalasia. The diagnosis had been proven by barium swallow and esophageal manometry. Therapy was carried out endoscopically between June 1996 and December 1998 by injection of 25 mouse units (MU) botulinum toxin into each of the four quadrants of the lower esophageal sphincter (LES). Lower esophageal sphincter pressure (LESP) was measured prior to and 1 week after endoscopic therapy. A standardized questionnaire was used for symptom assessment, at the initial presentation, at 1 week and at 2.5 +/- 0.8 years after treatment. The LESP was significantly reduced (pre-treatment 62.1 +/- 15.2 mmHg vs. post-treatment 43.1 +/- 12.5 mmHg; P < 0.01). Symptoms improved in 16 patients (pre-treatment symptom score 9.5 +/- 2.9 vs. post-treatment symptom score 4.7 +/- 1.8; P < 0.01). Nine patients showed no relevant improvement. From the 16 patients with a good initial response, two were lost to follow-up. In nine patients the outcome was still satisfactory after a mean of 2.5 years (1.5 - 4 years) (pre-treatment symptom score 9.5 +/- 2.9 vs. symptom score at 2.5 years after Botox 5.1 +/- 1.5; P < 0.05). These patients were on average 67.7 +/- 12.5 years old. The remaining five patients received a second or third injection of botulinum toxin, but none improved substantially for more than 6 months. One of them eventually underwent pneumatic dilation, and three laparoscopic myotomy. Thus, botulinum toxin treatment was unsuccessful in 14 patients in all. These 14 patients were, on average, significantly younger than the nine successfully treated patients (46.1 +/- 12.6 years vs. 67.7 +/- 12.5 years; P < 0.01) and had significantly higher LESP values prior to botulinum toxin therapy (72.8 +/- 8.9 mmHg vs. 47.8 +/- 9.2 mmHg; P < 0.01). The long-term success of botulinum toxin injection into the LES in patients with achalasia is highest in elderly patients and in patients with an LESP not exceeding the upper normal level prior to treatment by 50 % or more. On the basis of our results, younger patients (< 55 years) with a severe increase in LESP do not seem to benefit from botulinum toxin injection and pneumatic dilation or myotomy may be more advantageous to them.

ESOPHAGEAL DYSMOTILITY OF PATIENTS WITH DYSPHAGIA DURING MEALS

We investigated the relationship between dysphagia during meals and esophageal motility in 53 patients (23 men and 30 women, average age 52.8±17.5 years, mean±SD, 19-92 years) without endoscopic abnormal findings aside from atrophic gastritis. Esophageal manometry was performed using the intraluminal microtransducer method. Resting lower esophageal sphincter (LES) pressure was assessed by the rapid pull-through method. Esophageal contraction after 10 repeated 5-ml water swallowings separated by 30 seconds was measured at 3, 8, 13, and 18cm above LES. In 53 patients with dysphagia, 40 (75.5%) showed esophageal dysmotility. Twenty-three patients with esophageal dysmotility had a typical motility disorder (classic achalasia, 5 patients ; vigorous achalasia, 3 patients ; diffuse esophageal spasm, 10 patients ; nutcracker esophagus, 4 patients ; hypertensive esophagus, 1 patient). Seventeen patients with esophageal dysmotility had non-specific esophageal motility disorder (NEMD). An increase in the severity of dysphagia was paralleled by a significantly increased prevalence of esophageal dysmotility. The remain-ing 13 patients did not have abnormal findings on esophageal manometry. Mean amplitudes 3 cm above LES in patients with NEMD were significantly lower than those of controls. The frequency of primary peristalsis in patients with NEMD was significantly lower than that of controls. The present results suggest that esophageal dysmotility contributes to dysphagia during meals in patients with dysphagia without endoscopic abnormal findings aside from atrophic gastritis.

Use of botulinum toxin as a diagnostic/ therapeutic trial to help clarify an indication for definitive therapy in patients with achalasia

OBJECTIVE: Intrasphincteric injection of botulinum toxin is useful in achalasia but is limited by its short term efficacy. The aim of this study was to evaluate the use of botulinum toxin in selected patients in whom its short duration of action may be useful in guiding therapy before considering more invasive procedures that might not be indicated. METHODS: Over a 3 yr period, botulinum toxin was injected into the lower esophageal sphincter in patients with: 1) symptoms consistent with achalasia but insufficient manometric criteria to make the diagnosis; 2) complex clinical situations in which there were factors in addition to achalasia that may be contributing to the patient’s symptoms and that required different treatment; 3) atypical manifestations of achalasia; 4) advanced achalasia in which it was unclear that sphincter-directed therapy ( vs esophagectomy) would be of benefit; and 5) after Heller myotomy. Clinical response was assessed mostly by symptom improvement, but in some patients follow-up barium swallow or radioscintigraphy was available. RESULTS: Eleven patients were identified. Ten had complete symptomatic response to the injection. Two patients have undergone subsequent successful pneumatic dilation, one a successful laparoscopic myotomy, and another currently scheduled for surgical myotomy. The only patient without response had advanced achalasia requiring esophagectomy. CONCLUSIONS: Intrasphincteric injection of botulinum toxin into the lower esophageal sphincter is a useful and safe means of guiding therapy in those patients with a variant of achalasia, atypical achalasia, or complex achalasia in which it is unclear that more invasive procedures such as pneumatic dilation or surgical myotomy are the correct therapy.

Outcome after laparoscopic fundoplication is not dependent on a structurally defective lower esophageal sphincter

With the advent of laparoscopic surgery and the recognition that gastroesophageal reflux disease often requires lifelong medication, patients with normal resting sphincter characteristics are now being considered for surgery. The outcome of these patients after fundoplication is unknown and formed the basis of this study. The study population consisted of 123 patients undergoing laparoscopic Nissen fundoplication between 1992 and 1996. All patients had increased esophageal acid exposure on 24-hour esophageal pH monitoring. Patients were divided into those with a normal (n = 36) and those with a structurally defective (n = 87) lower esophageal sphincter (LES), based on LES resting pressure (normal >6 mm Hg), overall length (normal >2 cm), and abdominal length (normal >1 cm), and their outcomes were assessed. Each group was subsequently divided into patients presenting with a primary symptom that was “typical” (heartburn, regurgitation, or dysphagia) or “atypical” (gastric, respiratory, or chest pain) of gastroesophageal reflux, and outcome was assessed. Median duration of follow-up was 18 months after surgery. Overall, laparoscopic fundoplication was successful in relieving symptoms of gastroesophageal reflux in 90% of patients. Patients with a typical primary symptom had an excellent outcome irrespective of the resting status of the LES (95% and 97%, respectively). Atypical primary symptoms were significantly more common in patients with a normal LES (29%) than in those with a structurally defective LES (10%; P <0.05), and these symptoms were less likely (50%) to be relieved by antireflux surgery. Laparoscopic antireflux surgery is highly successful and not dependent on the status of the resting LES in patients with increased esophageal acid exposure and primary symptoms “typical” of gastroesophageal reflux. Antireflux surgery should be applied cautiously in patients with atypical primary symptoms.

The role of motilin and cisapride in the enteric nervous system of the lower esophageal sphincter in humans.

To assess the pharmacophysiological significance of the enteric nervous system and the responses of the human lower esophageal sphincter (LES) to motilin and cisapride, the mechanical responses of esophageal tissues from six patients with esophageal cancer and seven patients with gastric cancer were investigated. Circular muscle reactions were recorded to evaluate the in vitro esophageal responses to electrical field stimulation (EFS), motilin, and cisapride, evoking the adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. The findings of this study revealed that: cholinergic nerves are mainly involved in the regulation of enteric nerves in the steady state, while non-adrenergic non-cholinergic (NANC) inhibitory nerves also exist; motilin may act both via nerves and also directly on the LES smooth muscle; and cisapride releases acetylcholine from the end of the postganglionic fiber of the cholinergic nerve in human LES thereby inducing contraction of the LES. These results suggest that cholinergic and NANC inhibitory nerves play an important role in human LES, and that motilin and cisapride is clinically useful for improving the impaired LES of patients with gastroesophageal reflux.

Three-dimensional imaging of the lower esophageal sphincter in healthy subjects and gastroesophageal reflux.

The resting pressure and intraabdominal length are the most important factors which determine competence of the lower esophageal sphincter (LES). The intraabdominal sphincter vector volume (ISVV) is a single value which takes into account both of these measurements. Normal values of ISVV and of the total sphincter vector volume (TSVV) were established in 20 normal subjects. The sensitivity and the specificity of ISVV and TSVV were then evaluated in 81 patients with gastroesophageal reflux disease (GERD) and in 19 normal subjects and were compared with the usual stepwise pullback manometry (SPM) measuring the resting pressure of the LES at the respiratory inversion point. The motorized pullthrough technique was used to perform the vector volume procedure. Normal values of ISVV were 1870-10740 mm Hg2 x mm, and of TSVV 2200-13110 mm Hg2 x mm. The sensitivity of ISVV was 93.8% (p < 0.05), of TSVV 80.2%, and of SPM 81.5%. The specificity of ISVV and TSVV was 89.5% and of SPM 78.9% (not significant). Analysis of the intraabdominal sphincter vector volume is more sensitive than the total sphincter vector volume or standard stationary manometry in establishing a defective LES in patients with GERD. Intraabdominal sphincter vector volume analysis will allow surgeons better to identify patients with a defective LES who may be suitable for antireflux surgery.

Botulinum toxin for achalasia: Long-term outcome and predictors of response

BACKGROUND & AIMS: Botulinum toxin injection into the lower esophageal sphincter of patients with achalasia results in effective short-term relief of symptoms. The aims of this study were to examine the long- term outcome of these patients and to determine the predictors of response to this therapy. METHODS: Thirty-one patients with achalasia treated with botulinum toxin were followed up prospectively for a median duration of 890 days. RESULTS: Twenty-eight patients improved initially, but only 20 patients had sustained improvement beyond 3 months; the latter patients were classified as responders. The response rate was greater in patients older than 50 years of age (82% vs. 43% in younger patients; P = 0.03) and in patients with vigorous achalasia (100% vs. 52% with classic achalasia; P = 0.03). Duration of illness, previous dilation, and baseline radiological characteristics did not influence outcome. Nineteen responders eventually had relapse after a median duration of 468 days (range, 153 - 840 days). Fifteen of these patients received a second injection with satisfactory results obtained in the majority of patients. CONCLUSIONS: Botulinum toxin is an effective treatment for achalasia in about two thirds of patients, with a duration of response averaging 1.3 years. Age and type of achalasia seem to be important predictors of response. (Gastroenterology 1996 May;110(5):1410-5)

High-resolution endoluminal sonography in achalasia

Background: Imaging of the lower esophageal sphincter in patients with achalasia using 7.5 and 12 MHz ultrasound transducers has shown variable results. Methods: A 20 MHz radial ultrasound transducer was used to quantitatively compare the lower esophageal sphincter in patients with achalasia to that of normal volunteers. The transducer, housed in a 6.2F catheter, was placed at the level of the lower esophageal sphincter in 29 patients with achalasia and 19 normal subjects. Videotaped images from the lower esophageal sphincter were digitized and the width of the circular smooth muscle, longitudinal smooth muscle, and total muscularis propria were measured. A mean width for each muscle layer was calculated. Results: All muscle layers were found to be significantly thickened at the lower esophageal sphincter in patients with achalasia when compared with those in normal subjects: circular smooth muscle (0.206 cm ± 0.137 cm vs 0.124 cm ± 0.038 cm, p < 0.017); longitudinal smooth muscle (0.128 cm ± 0.077 cm vs 0.088 cm ± 0.028 cm, p < .041); and total muscle thickness (0.317 ± 0.180 cm vs 0.224 cm ± 0.049 cm, p < 0.033). Conclusion: Although high-resolution endoluminal sonography cannot be used to differentiate patients with achalasia from normal controls, this study quantitatively demonstrates that both the mean longitudinal and mean circular smooth muscle layers at the lower esophageal sphincter are wider in patients with achalasia than in a group of normal subjects. (Gastrointest Endosc 1995;42:545-9.)

Erythromycin strengthens the defective lower esophageal sphincter in patients with gastroesophageal reflux disease

Motilio induces phase III activity of the gastrointestinal tract. Erythromycin has a motilin-like effect on the stomach and significantly increases the lower esophageal sphincter (LES) pressure in normal volunteers. This investigation was performed to evaluate the effects of erythromycin on esophageal function in patients with gastroesophageal reflux disease (GERD). Esophageal manometry was performed in 10 GERD patients before and after intravenous infusion of 500 mg of erythromycin. Values are expressed as mean ± SEM. LES pressure increased from 13.9 ± 2.9 mm Hg at baseline to 28.9 ± 3.6 mm Hg after infusion of erythromycin (p < 0.01). The duration of contractions in the proximal, middle, and distal esophagus was significantly prolonged from 3.5 ± 0.4 seconds, 3.8 ± 0.4 seconds, and 4.1 ± 0.5 seconds to 4.2 ± 0.2 seconds, 4.6 ± 0.5 seconds, and 5.6 ± 0.6 seconds, respectively, after infusion of erythromycin (p < 0.05 for each comparison). Erythromycin did not effect esophageal body contraction amplitude or velocity, or the upper esophageal sphincter. Serum motilin decreased slightly after the administration of erythromycin. We concluded the following: (1) Erythromycin profoundly stimulates the defective LES in patients with GERD. This appears to be a direct motilin agonist-like effect rather than being mediated by release of endogenous motilin. (2) Erythromycin has less effect on the esophageal body, although it does prolong the duration of esophageal contractions.

The Cohen test does not predict outcome in achalasia after pneumatic dilation.

The Cohen test has been recommended to evaluate the efficacy of pneumatic dilation of the lower esophageal sphincter in patients with achalasia. It consists of ingestion of 8 ounces of heavy barium. Upright radiographs are performed 5 minutes later to determine the height of the barium column in the esophagus in relation to the diaphragm. A column less than 1 cm above the diaphragm is a negative test indicating successful dilation and the high probability of dysphagia resolution. A positive Cohen test, a column exceeding 1 cm, is said to correlate with persistent symptoms and need for redilation. We evaluated this in a prospective manner for a 6-year period. Twenty-eight patients underwent standard technique pneumatic dilation at our institution. Achalasia was confirmed in all patients by way of upper endoscopy and manometry. A Cohen test was performed in all patients. Post-dilation symptoms and weight were analyzed at follow-up 6 weeks after dilation. Contrary to the original report, relief of dysphagia after dilation was not related to the results of the Cohen test (p = 0.77). A positive Cohen test was inversely correlated with both symptom duration (0.037) and lower esophageal sphincter pressure before dilation (p = 0.005). Weight gain after dilation was unrelated to Cohen test results (p = 0.67). We conclude that the Cohen test is not an accurate predictor of symptom relief after dilation and do not recommend its use to determine the end point of therapy in patients with achalasia.

Characteristics and Frequency of Transient Relaxations of the Lower Esophageal Sphincter in Patients With Reflux Esophagitis

Electromyogram of the submental muscles, esophageal manometry, and pH studies were simultaneously performed in an unselected group of 12 patients with subjective and objective evidence of gastroesophageal reflux (GER) disease to determine the frequency of transient relaxation of the lower esophageal sphincter (LES) and mechanisms of GER. Findings from these patients were compared with data from 10 asymptomatic healthy volunteers. Recordings were obtained for 1 h in the fasting state and 3 h after a standard 850-kcal meal. Transient relaxation of the LES was the only mechanism of acid reflux in normal subjects and accounted for 73.0% of the episodes of acid reflux in patients with GER disease. In both normal subjects and patients with GER, a large number of transient relaxations were associated at their onset with an attenuated submental EMG complex, a small pharyngeal contraction, and an esophageal contraction. The incidences of these associated events were similar in the two study populations. The frequency of transient relaxation of the LES in patients with GER was identical to that of controls. The frequency did not differ even in 9 patients with GER disease who had endoscopic esophagitis. Thirty-six percent of transient relaxations in the normal subjects were accompanied by pH evidence of reflux, but in the GER patients with endoscopic esophagitis 65% of the transient LES relaxations resulted in a reflux event. Acid reflux at the moment of deep inspiration was the second most common mechanism of GER in our patients. Four patients who demonstrated this mechanism had hiatal hernias and more severe esophagitis than the rest of the group. Our findings confirm that transient relaxation of the LES is the major mechanism of GER in patients with reflux esophagitis. However, the similar frequency of this relaxation in GER patients and in healthy asymptomatic subjects suggests that factors other than transient LES relaxation play an important role in the pathogenesis of GER disease.

Regulatory peptides in the lower esophageal sphincter of man.

Smooth muscle specimens were taken from the lower esophageal sphincter of patients suffering from achalasia or hiatus hernia with gastro-esophageal reflux. The specimens were analysed for neurohormonal peptides using immunochemistry and immunocytochemistry. Control specimens were obtained from patients subjected to esophageal resection because of esophageal cancer. The concentration of vasoactive intestinal polypeptide (VIP) was higher and the VIP nerve supply greater in patients with hiatus hernia than in control patients. The VIP nerve supply and the content of this peptide was lower in patients with achalasia than in controls. The same tendency was observed for substance P and enkephalin although the changes in their concentrations were not statistically significant. Enkephalin fibers were few, both in specimens from control patients and from patients with hiatus hernia; they could not be detected in specimens from patients with achalasia. Never fibers containing somatostatin or gastrin/cholecystokinin could not be detected in any of the groups and somatostatin and gastrin/cholecystokinin could not be measured in extracts of the lower esophageal sphincter. We propose that changes in the concentration of neuropeptides may at least contribute to manifestations of achalasia and of decreased lower esophageal sphincter pressure and gastro-esophageal reflux.

EXPERIMENTAL AND CLINICAL STUDIES ON THE LOWER ESOPHAGEAL SPHINCTER IN REFERENCE TO ITS ASYMMETRY AND TO THE EFFECTS OF RESPIRATION, POSTURE AND GASTRIC CONTENTS

The present study was designed to investigate basic and clinical problems of intraluminal lower esophageal sphincter (LES) manometry. As for the basic study, manometry apparatuses, measuring conditions and methods were revalued. For clinical study, effects of gastric contents and gastrin were studied with special reference to the asymmetry of the LES. The results obtained may be summarized as follows: Occlusion test performed in a LES model and dogs showed that the rate of pressure increase was greater in proportion to the greater perfusion rate as well as to smaller calibre of the manometry tube. The lower esophageal sphincter pressure (LESP) became greatest when the perfusion rate was increased up to a certain level and also when the withdrawal speed of a manometry tube was slowed down to a certain speed. Analysis of LES from the point of respiratory reversal disclosed that the pressure was greatest at the direction of 8 o'clock followed by those at 0 and 4 o'clock. The length of LES was longest at 4 o'clock followed by those at 0 and 8 o'clock. These differences in length of LES was mostly in accordance with the length of LES caudal to the point of respiratory reversal. LESP measured in different postures was greatest in the prone position suggesting the effect of intraabdominal pressure. Intragastric instillation of saline resulted in increase of intragastric pressure and LESP. Asymmetry of the LES in patients with sliding hiatal hernia, esophageal varices and achalasia showed profiles specific to the individual lesion.