Reduction In Lower Oesophageal Sphincter Pressure Research Articles

Redo Laparoscopic Heller's Cardiomyotomy for Recurrent Achalasia: Is Laparoscopic Surgery Feasible?

Achalasia cardia is an esophageal motor disorder with raised lower esophageal sphincter (LES) pressure. Minimally invasive procedures have become the procedure of choice compared with conventional open surgery. After the primary surgery, recurrence or persistent symptoms have been noted in almost 10%-20% of cases. In this case series, we share our experience with a series of 7 patients who presented to us from January 2010 to January 2017 for recurrent symptoms, following Heller's myotomy for achalasia cardia. Commonest symptom of recurrence was dysphagia with mean duration of recurrence of 17.9 months between primary and redo surgery. Revisional Heller's myotomy with Dor's fundoplication was performed in all patients laparoscopically. Mean duration of surgery was 150 minutes. Incomplete gastric myotomy and fibrosis at previous myotomy scar were the main causes of recurrence. Mean duration of hospital stay was 3.5 days. Mean follow-up period was 23.5 months. All the patients were symptomatically better following the redo surgery. Subsequent manometry was performed at the end of 3 months with mean reduction in LES pressure of 7.5 + 1.2 mmHg. Laparoscopic redo Heller's cardiomyotomy is a possibly reasonable option with good long-term results and minimal postoperative complications in expert hands.

PTU-017 Per Oral Endoscopic Myotomy (POEM) for Achalasia

Introduction Achalasia is an oesophageal motor disorder due to inhibitory neuron dysfunction, resulting in loss of oesophageal peristalsis and impaired lower oesophageal sphincter relaxation. POEM is emerging as a viable alternative to laparoscopic Heller’s myotomy (LHM) for the treatment of achalasia. However, it is still in it’s infancy in the West with no reported cases from UK. We aim to present two videos and discuss the technical details of the procedure in a simple type II achalasia and in a complex sigmoid achalasia. Methods Prior to undertaking POEM patients are investigated with barium swallow, gastroscopy and high-resolution manometry to confirm the diagnosis of achalasia and delineate the anatomy of the oesophagus. Eckhardt score is calculated pre and post POEM. Informed consent is undertaken, including alternatives to POEM: LHM, pneumatic dilatation and Botox injection. The procedure steps include (video): 1. Submucosal injection and incision 2. Creation of submucosal tunnel 3. Endoscopic myotomy 4. Closure of mucosal entry. Results Case 1: A 61 year-old lady, presenting with dysphagia, retrosternal chest pain and regurgitation (Eckhardt score 6). Barium swallow demonstrated typical appearances of achalasia (see video). Pre-POEM manometry confirmed Type II achalasia with a resting lower oesophageal sphincter (LOS) pressure of 26. She underwent an uneventful POEM procedure via the anterior approach using a combination of flush-knife and triangular tip knife to achieve a 10+4 cm myotomy. On follow-up she has no symptoms (Eckhardt score 0) and repeat manometry shows a reduction in LOS pressure to 15. Case 2: A 52 year-old lady, presenting with dysphagia, retrosternal chest pain, regurgitation and weight loss (Eckhardt score 11). Barium swallow demonstrated advanced achalasia with severe dilatation and a sigmoid appearance (see video). She was treated at her local centre with two sessions of PD and one of Botox despite which she suffered ongoing symptoms. Pre-POEM manometry revealed Type II achalasia and an LOS pressure of 25.5. She underwent an uneventful POEM procedure via the posterior approach using the O-type Erbe hybrid knife to achieve an 11 + 4 cm myotomy. Significant fibrosis was encountered due to previous intervention. On follow-up her symptoms improved significantly. Repeat manometry is awaited. Conclusion Here we describe the technique of POEM at the two ends of the disease spectrum of achalasia We demonstrate the feasibility of the technique in the hands of a UK Endoscopist. We demonstrate two different approaches to POEMS (Anterior vs Posterior) and with two different knives and will discuss the Pros and Cons of these approaches. Despite previous intervention and submucosal fibrosis, POEM is still a viable treatment for patients with ongoing symptoms. Disclosure of Interest None Declared

OC-044 Effects of Sleeve Gastrectomy on Gastro-Oesophageal Reflux and Oesophago-Gastric Motility

Introduction Sleeve gastrectomy is increasingly used as both a definitive and staggered weight loss procedure. The effect of sleeve gastrectomy on gastro-oesophageal reflux (GOR) remains uncertain. We studied the effect of sleeve gastrectomy on GOR, pressure parameters at the Lower Oesophageal Sphincter (LOS), oesophageal and gastric motility. Methods Sixteen patients (median age 46 (range 25–71)) with morbid obesity underwent high resolution oesophageal manometry and 24hr ambulatory pH-impedance monitoring, at least 2 weeks pre-op and 3 months post sleeve gastrectomy (median no. of days post-op 129 (range 84–202)). All patients documented reflux and dysphagia symptoms at the time of testing. Nine patients also underwent concurrent gastric emptying with 13C labelled octanoate breath test. Parametric data was analysed using the paired t-test and non-parametric data with Wilcoxon matched pairs test. Results Mean Body Mass Index (BMI) fell from 49 (41.3–58.3) to 38.5(35–46.3). 5/16 patients reported new or worsening reflux symptoms (31%). Basal LOS pressure fell from 14.4mmHg (9.7–28.5) pre-op to 8.9mmHg (0.7–40.5) post-op (p Conclusion Both acid and non-acid gastro-oesophageal reflux is increased after sleeve gastrectomy with 31% of patients developing de novo acid reflux post-op. This is despite a reduction in BMI and accelerated gastric emptying. A reduction in LOS pressure and increased G-O pressure gradient are likely to be contributing factors. Future studies should determine whether decreased gastric compliance stimulates increased numbers of transient lower oesophageal sphincter relaxations. Disclosure of Interest None Declared

Presentation, Diagnosis, and Management of Achalasia

Presentation, Diagnosis, and Management of Achalasia

Laparoscopic treatment for esophageal achalasia: experience at a single center.

Achalasia is a not frequent esophageal disorder characterized by the absence of esophageal peristalsis and incomplete relaxation of the lower esophageal sphincter (LES). Its cause is unknown. The aim of treatment is to improve the symptoms. We report the results of the treatment of this condition achieved in one center. We conducted a retrospective study of patients with esophageal achalasia. In the period 2010-2012 we observed 64 patients, of whom 19 were referred for medical treatment. Three of the remaining patients underwent botulinum toxin injection, 17 underwent multiple endoscopic dilation procedures and 25 underwent laparoscopic surgery. There were no complications in the group undergoing endoscopic therapy, but symptom remission was only temporary. Patients undergoing surgery showed a significant improvement in symptoms and no recurrence throughout the follow-up period, that is still ongoing (3 years). There were no major complications in any case and no morbidity or mortality. Surgical treatment of esophageal achalasia with laparoscopic Heller myotomy and Dor fundoplication gives the best and longest-lasting results in suitably selected patients. The extension of the myotomy and reduction in LES pressure are the most important parameters to achieve a good result.

The Impact of Gastric Distension on the Lower Esophageal Sphincter and Its Exposure to Acid Gastric Juice

The lower esophageal sphincter (LES) in patients with gastroesophageal reflux disease often has a low resting pressure and a short abdominal length. The mechanism by which this occurs is unknown. We hypothesize that gastric distension causes progressive effacement of the abdominal portion of the LES, exposing it to acid injury resulting in mucosal and sphincter damage. Our aim was to assess in normal subjects the effect of gastric distension on the LES length and pressure and its exposure to acid gastric juice. Eleven asymptomatic volunteers had their LES length and pressure measured before and during gastric distension. The location of the pH step-up point (shift from gastric pH to a pH >4) was also measured before and after distension. Progressive gastric distension with air resulted in progressive shortening of LES (R = 0.89, P < 0.0001). After infusion of 750 cc of air there was a significant reduction in the median LES length from 4 to 2.6 cm (P = 0.001). This change occurred in the abdominal length of the LES (2.6-1.4 cm [P = 0.001]) and not in the thoracic length. At rest the pH step-up point was 0.5 cm above the lower border of the LES and with distension moved a median of 1 cm cephalad within the LES. Simultaneously with the loss of length there was a reduction in LES pressure (27.4-23.4 mm Hg, P = 0.02). Gastric distension causes progressive shortening of the abdominal length of the LES and a reduction in its pressure. The process exposes the effaced mucosa and sphincter to acid gastric juice.

T1247 Effects of Chenodeoxycholic Acid On Gastrointestinal and Colonic Transit and Bowel Function in Healthy Volunteers

INTRODUCTION: Epidemiologic evidence suggests a link between gastro-esophageal reflux disease (GERD) and obesity. Studies suggest that this relationship is due to the effects of central adiposity on intragastric pressure with disruption of the gastro-esophageal junction (GEJ) reflux barrier, however the clinical relevance of these findings has not been proven. METHODS: From Aug 2005 to Dec 2006, patients sent to a referral center for physiologic investigation of GERD were studied. Height, weight and waist circumference (WC) were measured. Stationary manometry and 24hr ambulatory pH studies off acid-suppressants were performed and symptom severity was assessed by a validated questionnaire. Linear regression models were used to analyze associations between covariates of interest and Pearson's correlation coefficient (PC) was applied to assess the strength of association. RESULTS: 582/676(86%) consecutive patients (age 48 (range 14-89), 56% female) had complete data for analysis. The prevalence of obesity defined by BMI≥30kg.m-2 in males and females was 16% and 23% (p=ns) respectively. More men hadWC≥99cm (M41%:F28%; p<0.001)). %time pH<4 at 5cm above the lower esophageal sphincter (LES) increased with obesity (PC=0.255 and 0.240 for BMI and WC respectively; both p<0.001) and age (PC= 0.162; p<0.001) and was higher in men than women (p=0.014) Increase in %time pH<4 was associated with a reduction in LES pressure and abdominal LES length (PC=-0.327, -0.344 respectively; p<0.001). There was a weak negative association of BMI with LES pressure (PC=-0.140; p=0.005) but no link with abdominal LES length. In contrast, there was a significant negative association of WC with LES pressure (PC=-0.225; p<0.001) and abdominal LES length (PC=-0.213; p<0.001). Overall symptom severity increased with %time pH<4 (PC=0.209; p<0.001); however there was no change in symptom severity with BMI (PC=0.056, p=0.17) and the effect of WC was weak and of borderline significance (PC=0.083, p=0.05). CONCLUSION: In this large cohort of clinical patients referred for investigation of reflux symptoms, gastro-esophageal reflux increased with obesity and was most prevalent in elderly males with central adiposity. WC but not BMI was associated with both reduced LES pressure and abdominal length. These findings confirm the mechanistic link between increasing WC and the risk of reflux via raised intragastric pressure and disruption of the GEJ. In contrast, there was little change in symptom severity despite increased acid exposure in this group. The relative insensitivity to acid reflux may explain the increased prevalence of severe and complicated reflux in obese patients.

T1246 The Effect of Central Adiposity On Esophageal Acid Exposure and Symptoms of Gastro-Esophageal Reflux Disease

INTRODUCTION: Epidemiologic evidence suggests a link between gastro-esophageal reflux disease (GERD) and obesity. Studies suggest that this relationship is due to the effects of central adiposity on intragastric pressure with disruption of the gastro-esophageal junction (GEJ) reflux barrier, however the clinical relevance of these findings has not been proven. METHODS: From Aug 2005 to Dec 2006, patients sent to a referral center for physiologic investigation of GERD were studied. Height, weight and waist circumference (WC) were measured. Stationary manometry and 24hr ambulatory pH studies off acid-suppressants were performed and symptom severity was assessed by a validated questionnaire. Linear regression models were used to analyze associations between covariates of interest and Pearson's correlation coefficient (PC) was applied to assess the strength of association. RESULTS: 582/676(86%) consecutive patients (age 48 (range 14-89), 56% female) had complete data for analysis. The prevalence of obesity defined by BMI≥30kg.m-2 in males and females was 16% and 23% (p=ns) respectively. More men hadWC≥99cm (M41%:F28%; p<0.001)). %time pH<4 at 5cm above the lower esophageal sphincter (LES) increased with obesity (PC=0.255 and 0.240 for BMI and WC respectively; both p<0.001) and age (PC= 0.162; p<0.001) and was higher in men than women (p=0.014) Increase in %time pH<4 was associated with a reduction in LES pressure and abdominal LES length (PC=-0.327, -0.344 respectively; p<0.001). There was a weak negative association of BMI with LES pressure (PC=-0.140; p=0.005) but no link with abdominal LES length. In contrast, there was a significant negative association of WC with LES pressure (PC=-0.225; p<0.001) and abdominal LES length (PC=-0.213; p<0.001). Overall symptom severity increased with %time pH<4 (PC=0.209; p<0.001); however there was no change in symptom severity with BMI (PC=0.056, p=0.17) and the effect of WC was weak and of borderline significance (PC=0.083, p=0.05). CONCLUSION: In this large cohort of clinical patients referred for investigation of reflux symptoms, gastro-esophageal reflux increased with obesity and was most prevalent in elderly males with central adiposity. WC but not BMI was associated with both reduced LES pressure and abdominal length. These findings confirm the mechanistic link between increasing WC and the risk of reflux via raised intragastric pressure and disruption of the GEJ. In contrast, there was little change in symptom severity despite increased acid exposure in this group. The relative insensitivity to acid reflux may explain the increased prevalence of severe and complicated reflux in obese patients.

American Gastroenterological Association Institute Technical Review on the Management of Gastroesophageal Reflux Disease

American Gastroenterological Association Institute Technical Review on the Management of Gastroesophageal Reflux Disease

Long-term clinical results of thoracoscopic Heller's myotomy in the treatment of achalasia☆

The aim of this study is to review the immediate and long-term results of video-imaged thoracoscopic Heller's myotomy (THM). All patients undergoing THM by a single surgeon at one institution were analysed. Follow-up was conducted using a structured questionnaire and oesophageal manometry and/or 24h pH monitoring were undertaken when clinically indicated. Fifty-six consecutive patients (32 males, 24 females, mean age 45+/-18.7 years) suffering from grade 4 dysphagia underwent THM between January 1992 and March 2006. Preoperative mean lower oesophageal sphincter (LOS) pressure was 38.4+/-10.6 mmHg. Eighteen patients (32.1%) had undergone previous pneumatic dilatations. There were no hospital deaths. Oesophageal perforation occurred in two patients; one repaired thoracoscopically and one at thoracotomy. Mean hospital stay was 4+/-1.37 days. At mean follow-up of 5.9+/-4.66 years, freedom from any reintervention was 87% (49/56). Twenty-nine patients (52%) were asymptomatic. In patients with residual or recurrent symptoms (n=27), their severity was significantly reduced from the preoperative period (dysphagia score 1.37+/-0.77 vs 4.00+/-0; p<0.001). Seven patients (12.5%) with troublesome residual or recurrent grade 3-4 dysphagia underwent repeat oesophageal manometric study, showing a mean reduction in LOS pressure from their baseline values of 46.8+/-6.1-30.0+/-5.4 mmHg (p<0.001). Of these patients, three patients with grade 4 dysphagia were reoperated: one open Heller's myotomy and two by cardia resection. Eleven patients complained of troublesome postoperative heartburn; distal oesophageal acid exposure was shown to be abnormal in nine patients (16.9%) and all were successfully managed with medical therapy. The results of thoracoscopic treatment for achalasia are at least equivalent to historical outcomes obtained with open surgery but the patient is spared major thoracotomy or the acid reflux associated with a laparoscopic approach.

Achalasia: botox, dilatation or laparoscopic surgery in 2006

Achalasia is a primary oesophageal motor disorder characterized by insufficient relaxation of the lower oesophageal sphincter (LOS) and loss of oesophageal peristalsis in the body. Despite some insight into the pathophysiology of this syndrome, much remains unknown, particularly with respect to its aetiology. It is not surprising, therefore, that the treatment of achalasia is entirely palliative and consists of different methods to reduce LOS tone and thereby relieve functional obstruction to oesophageal transit. Reduction in LOS pressure can be achieved either by traditional smooth muscle relaxants, chemical denervation (i.e. botulinum toxin), brusque (usually pneumatic) dilation or surgical myotomy. These methods vary in their level of invasiveness and risk of adverse effects which, in general, correlate well with long-term efficacy. Thus, conventional smooth muscle relaxants such as calcium channel blockers or nitrates seldom yield satisfactory long-term alleviation of symptoms; however, this option can be used on an as-needed basis pending investigations and during the planning stage for more definitive therapy. In this article, we will focus on three most frequent options for treatment of achalasia, botulinum toxin injection, pneumatic dilation and surgical myotomy. Further, we have chosen a somewhat unconventional question and answer format to give it a practical patient-oriented flavour, instead of a more theoretical and comprehensive traditional discussion, for which the reader is referred to several thorough reviews published recently. We have also chosen not to enter into discussions of costeffectiveness and economic analysis, not only because of a lack of a clear-cut answer in the literature, but also because this is seldom a consideration from an individual patient’s perspective.

Long-Term Follow-Up after Pneumatic Dilation for Achalasia Cardia: Factors Associated with Treatment Failure and Recurrence

Though most patients with achalasia cardia (AC) respond to pneumatic dilation (PD), one-third experienced recurrence. Long-term follow-up studies on factors associated with various outcomes are scanty. In this retrospective study, 126 patients (36.5 +/- 14.6 yr, 76 male) with AC (diagnosed by esophagoscopy, barium esophagogram, and/or manometry) were followed up in person or through mail. The median dysphagia-free duration was calculated by Kaplan-Meier analysis. Factors associated with nonresponse and recurrence after PD were determined using univariate and multivariate analyses. Symptoms were dysphagia (126, 100%), chest pain (21, 17%), regurgitation (61, 48%), weight loss (33, 26%), and pulmonary symptoms (23, 18%); 5 of 126 (4%) had megaesophagus (> or =7 cm). The mean lower esophageal sphincter (LES) pressure was 38.7 +/- 16.8 mmHg. One hundred and fifteen of 126 (91%) patients responded to PD (90 (71%) to first session); 25 of these had recurrence of dysphagia after 15 +/- 17 months. Post-PD chest pain requiring hospitalization occurred in 21 of 126 (17%; one had an esophageal perforation). Post-PD LES pressure, which was assessed in 48 of 126 patients, had decreased by >50% from baseline in 14 of 29 responders, 0 of 11 nonresponders (p= 0.004, chi(2) test), and 5 of 8 relapsers. The median dysphagia-free duration by Kaplan-Meier analysis was 60 months (SE 2.7, 95% CI 54.7-65.3). On univariate analysis, male gender, pulmonary symptoms (nocturnal coughing spell, history of respiratory infection), absence of chest pain, and failure to achieve a reduction in LES pressure >50% after PD were associated with poor outcome; whereas age, grade of dysphagia, regurgitation, megaesophagus, and LES pressure before PD were not. Male gender was associated with poor outcome by multivariate-analysis. PD is an effective and safe treatment for AC. Post-PD LES pressure measurement may be helpful in assessing response. Male patients have poorer outcomes following PD.

Progress with novel pharmacological strategies for gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease (GORD) is a chronic disorder characterised by an increased exposure of the oesophagus to intragastric contents. Currently, GORD symptoms are maintained under control with antisecretory agents, mainly gastric proton pump inhibitors (PPIs). Although impaired oesophageal motility may partly underlie the pathophysiology of GORD, the use of prokinetic agents has been found to be unsatisfactory. To date, novel pharmacological approaches for GORD are mainly related to the control of transient lower oesophageal sphincter (LOS) relaxations (TLOSRs). The majority of patients with GORD have reflux episodes during TLOSRs, which are evoked by gastric distension, mainly occurring after ingestion of a meal. Patients with reflux disease with normal peristalsis and without or with mild erosive disease could potentially benefit from anti-TLOSR therapy. This therapy might also be of value to treat some severe forms of esophagitis in combination with PPIs. GABA-B-receptor agonists are the most promising class of agents identified so far for TLOSR control. The GABA-B-receptor agonist, baclofen, is the most effective compound in inhibiting TLOSRs in humans. Since baclofen has several CNS adverse effects, novel orally available GABA-B agonists are needed for effective and well tolerated treatment of GORD. Endogenous or exogenous cholecystokinin (CCK) causes a reduction in LOS pressure, an increase in TLOSR frequency and a reduction in gastric emptying. In healthy volunteers and patients with GORD, loxiglumide, a selective CCK1-receptor antagonist, was found to reduce the rate of TLOSRs, although its effect on postprandial acid reflux may be modest. Orally effective CCK antagonists are not marketed to date. The anticholinergic agent atropine, given to healthy volunteers and patients with GORD, markedly reduced the rate of TLOSRs. Because of severe gastrointestinal (and other) adverse effects of anticholinergics, including worsening of supine acid clearance and constipation, it is unlikely that this class of drugs will have a future as anti-TLOSR agents on a routine basis. In spite of their effectiveness in reducing TLOSR rate, untoward adverse effects, such as addiction and severe constipation, currently limit the use of morphine and other opioid mu-receptor agonists. The same applies to nitric oxide synthase inhibitors, which are associated with marked gastrointestinal, cardiovascular, urinary and respiratory adverse effects. Animal studies provide promising evidence for the use of cannabinoid receptor 1 agonists, by showing potent inhibition of TLOSRs in the dog, thus opening a new route for clinical investigation in humans. A better understanding of TLOSR pathophysiology is a necessary step for the further development of novel drugs effective for anti-reflux therapy.

Treatment of achalasia: the short-term response to botulinum toxin injection seems to be independent of any kind of pretreatment

BackgroundIt has been suggested that intrasphincteric injection of botulinum toxin (BTX) may represent an alternative therapy to balloon dilatation in achalasia. The aim of the present study was to test the effectiveness of botulinum toxin injections in achalasia patients, as assessed using lower oesophageal sphincter pressure (LOSP) and symptom scores, and to compare the response in patients with different types of pretreatment (no previous treatment, balloon dilatation, myotomy, BTX injection).MethodsForty patients who presented with symptomatic achalasia were treated with BTX injection (48 injections in 40 patients). Some of the patients had received prior treatment (seven with myotomy, seven with dilatation and eight with BTX). The symptoms were assessed using a global symptom score (0–10), which was evaluated before treatment, 1 week afterwards, and 1 month afterwards. Manometry was also carried out before and after treatment. Three different selections of patients were studied: all patients; untreated patients; and patients with prior BTX, dilatation, or myotomy.ResultsAfter BTX injection, there was a significant reduction in LOSP (before, 38.2 ± 11.3 mmHg; 1 week after, 20.5 ± 6.9 mmHg; 1 month after, 17.8 ± 6.8 mmHg; P < 0.001). The global symptom score and symptom subscores (dysphagia, regurgitation, chest pain) were significantly decreased after 1 week and 1 month. When the beneficial effects following BTX injection were compared (untreated vs. pretreated), neither changes in LOSP nor beneficial effects on the symptom scores significantly differed. After 6 months, 67.7% of all treated patients were still in symptomatic remission (subgroups: previously untreated patients, 61.5%, n = 26; prior dilatation, 71.4%, n = 7; prior myotomy, 71.4%, n = 7; prior BTX, 73.9%, n = 8).ConclusionsBTX injection offers an alternative treatment for achalasia which is safe and can be performed in an outpatient setting. The initial response to BTX, in terms of symptom scores and LOSP, appears to be independent of any prior treatment. A number of patients do not adequately respond to balloon dilatation or myotomy, which are the first-line treatment modalities in achalasia patients. BTX injection can be performed in these patients, and symptomatic benefit can be expected in the same percentages as with BTX injection in untreated patients.

Effect of Somatostatin on Lower Esophageal Sphincter Characteristics in Man

Somatostatin (SST) is known for its inhibitory effect on the gastrointestinal tract. Transient lower esophageal sphincter relaxations (TLESR), low or absent LES pressure (LESP) and swallow-induced LES relaxations are the most important reflux mechanisms. We have studied the effect of somatostatin on lower esophageal sphincter (LES) characteristics in man. Nine healthy volunteers participated in four experiments performed in random order and double-blind during continuous infusion of somatostatin (250 microg/h) or saline (control) under fasting and postprandial conditions. Esophageal motility was measured with sleeve manometry combined with pH metry. Under fasting conditions LESP was not influenced by somatostatin. Ingestion of the carbohydrate meal significantly (P < 0.01) decreased LESP. During continuous somatostatin infusion the postprandial decrease in LESP did not occur; LESP was even significantly (P < 0.05) increased over basal levels. Somatostatin did not significantly influence TLESR frequency, neither under basal conditions, nor postprandially. The residual pressure during swallow-induced LES relaxation was significantly (P < 0.05) increased by somatostatin. In humans somatostatin prevents postprandial reduction in LESP, does not affect TLESR, but inhibits swallow-induced LES relaxation.

Effect of medium- and long-chain triglycerides on lower esophageal sphincter pressure: role of CCK.

Fat meals are known to decrease lower esophageal sphincter (LES) pressure, possibly through postprandial CCK release. Dietary fat consists mainly of long-chain triglycerides (LCT), which potently stimulate CCK secretion. This effect contrasts with that of medium-chain triglycerides (MCT), which do not induce CCK release. We recorded LES pressure and gallbladder volume in six healthy subjects on five separate occasions during intraduodenal administration of 1) saline control, 2) LCT, 3) MCT, 4) LCT during intravenous infusion of the CCK receptor antagonist loxiglumide, and 5) MCT together with loxiglumide. LES pressure decreased significantly during administration of both LCT and MCT. Loxiglumide completely prevented the reduction in LES pressure during intraduodenal LCT, but not during intraduodenal MCT. Gallbladder volume decreased during LCT, but not during MCT. It is concluded that intraduodenal administration of equimolar amounts of both LCT and MCT significantly reduces LES pressure. The effect of LCT on LES pressure is mediated by CCK. The effect of MCT is not dependent on CCK, since MCT does not release CCK and loxiglumide does not prevent the MCT-induced reduction in LES pressure.

Effects of transdermal nicotine on lower esophageal sphincter and esophageal motility.

Cigarette smoking has been shown to decrease lower esophageal sphincter pressure (LESP) by 19-42%. This decrease in LESP may be due to nicotine in the cigarette smoke or substances other than nicotine. The aim of this study was to evaluate the effects of a nicotine patch on esophageal motility since nicotine patches are devoid of all toxins present in the cigarette smoke except the nicotine. Ten healthy nonsmoking volunteers underwent baseline esophageal manometry. Esophageal manometry was repeated after placing a nicotine transdermal patch (Nicotrol) designed to deliver 15 mg of nicotine per day. The parameters that were compared included LESP by rapid pull-through (LESP-RPT) and station pull-through (LESP-SPT), LES relaxation, and velocity, amplitude, and duration of esophageal contractions. Plasma nicotine and cotinine levels were measured prior to baseline manometry and after 12 hr of placing the nicotine patch, the LESP-RPT decreased by 31% from 17.4 +/- 6.1 to 12.1 +/- 3.3 (P = 0.013) and the LESP-SPT by 27% from 13.4 +/- 5.4 to 9.8 +/- 4.8 (P = 0.029) after the nicotine patch. LES relaxation was present in 100% before and after nicotine patch. There were no significant differences in velocity, duration, and amplitude of esophageal contractions after the nicotine patch. Plasma nicotine and cotinine was absent in all subjects at baseline but was significantly elevated after 12 hr of nicotine patch. Transdermal delivery of nicotine results in a significant reduction in LESP in healthy subjects without effecting LES relaxation or esophageal body motility.

Effect of cholecystokinin on lower oesophageal sphincter pressure and transient lower oesophageal sphincter relaxations in humans.

The effect of cholecystokinin (CCK) on the lower oesophageal sphincter (LOS) pressure, frequency of transient LOS relaxations, and the number of reflux episodes was investigated in six healthy subjects. LOS pressure was recorded on four separate occasions during continuous intravenous infusion of either saline or CCK-33 in doses of 0.25, 0.5, or 1.0 Ivy Dog units per kg body weight per hour (IDU.kg-1.h-1) for 90 minutes. Plasma CCK concentrations did not change during saline infusion, but increased significantly from 2.5 (0.3) pmol/l to steady state levels of 4.0 (0.4) pmol/l, 6.1 (0.4) pmol/l, and 9.3 (0.9) pmol/l respectively starting from 30 minutes. LOS pressure did not change significantly during infusion of saline or of CCK-33 at doses of 0.25 or 0.5 IDU.kg-1.h-1. However, a significant (p < 0.05) reduction in LOS pressure to a minimum level of 12 (4) mm Hg at 30 minutes compared with basal level (18 (4) mm Hg) and compared with saline was observed during infusion of CCK-33 at a dose of 1.0 IDU.kg-1.h-1. In addition, oesophageal motility and pH were recorded simultaneously in these six subjects on two separate occasions one hour before (fasting) and three hours during administration of a gastric load (dextrose 5%, pH 3) combined with continuous intravenous infusion of saline or CCK-33 at a dose of 1.0 IDU,kg-1.h-1. Plasma CCK concentrations did not change during the gastric load combined with saline, but increased significantly to a steady state level of 10.8 (0.8) pmol/l during intravenous infusion of CCK. The number of transient LOS relaxations increased significantly in the first hour during administration of the gastric load compared with fasting levels, both during saline infusion (fasting: 1.7 (0.6)/h, 1st hour: 4.3 (1.2)/h) and during CCK infusion (fasting: 1.7 (0.5)/h, 1st hour: 3.8 (0.7)/h). In the second and third hours the number of transient LOS relaxations fell to fasting levels in both experiments. No significant differences were observed in the number and type of transient LOS relaxations, mechanism of gastro-oesophageal reflux, or duration of acid exposure between the two experiments. It is concluded that in healthy subjects infusion of CCK-33 in a dose of 1.0 IDU.kg-1.h-1 significantly reduces LOS pressure but does not affect the frequency of transient LOS relaxations or acid exposure time during a continuous liquid gastric load.

Gastroesophageal reflux during gastrostomy feeding

Aspiration pneumonia is one of the most serious complications of gastrostomy tube feeding, with a reported incidence of 10%-20% in nursing home patients. The aims of this prospective study were to examine lower esophageal sphincter (LES) pressure before and after placement of gastrostomy tubes and to examine the effects of rapid intragastric bolus and slow, continuous feeding on LES pressure. Ten subjects were enrolled in the study. Basal LES pressure was measured before and after placement of gastrostomy tubes. Thereafter, LES pressure was measured for 15 minutes during rapid intragastric infusion of 250 mL of an enteral feeding formula and 100 mL water and continuous infusion of the enteral feeding formula at 80 mL/h. Scintigrams evaluating gastroesophageal reflux were obtained during each method of feeding. Placement of gastrostomy tubes had no effect on basal LES pressure. Rapid intragastric bolus infusion led to a reduction in LES pressure to incompetent levels at 2.1 +/- 2.0 mm Hg (P < 0.001). Free gastroesophageal reflux to the sternal notch was shown by scintigraphy. Slow, continuous gastrostomy feedings did not alter LES pressure (P > 0.05) or show free gastroesophageal reflux by scintigraphy. Gastroesophageal reflux and aspiration in patients fed via the gastrostomy tube may be caused by LES relaxation secondary to gastric distention caused by distention of the stomach.

Effect of cholestyramine and cholecystokinin receptor antagonist CR1505 (loxiglumide) on lower esophageal sphincter pressure in man.

Cholecystokinin (CCK) decreases lower esophageal sphincter pressure (LESP) in man. Cholestyramine, a nonabsorbable bile salt binding resin, stimulates endogenous CCK secretion. We have investigated the effect of oral ingestion of 16 g cholestyramine without and with infusion of the CCK receptor antagonist CR1505 (loxiglumide, 15 mg/kg/90 min) on LESP in seven healthy subjects. LESP was recorded for 90 min, in 10-min intervals, with the pull-through technique using a four-lumen water-perfused catheter. Oral ingestion of cholestyramine resulted in a significant (P < 0.05) decrease in LESP, starting from 10 min and continuing during the entire experiment (basal LESP: 11.8 +/- 2 mm Hg, minimal value reached during cholestyramine: 7.3 +/- 1 mm Hg; P < 0.05). Pretreatment with loxiglumide completely antagonized the effect of cholestyramine on LESP. Infusion of loxiglumide without cholestyramine did not affect basal LESP. It is concluded that: (1) cholestyramine significantly reduces LESP; (2) this reduction in LESP does not occur after pretreatment with loxiglumide, indicating that cholestyramine influences LESP through CCK release; and (3) basal LESP is not regulated by CCK.