Efficacy of medical therapy and antireflux surgery to prevent Barrett's metaplasia in patients with gastroesophageal reflux disease.
(73/633)
OBJECTIVE: To investigate whether Barrett's metaplasia may develop despite effective medical therapy. SUMMARY BACKGROUND DATA: Gastroesophageal reflux disease has a multifactorial etiology. Therefore, medical treatment may not prevent complications of reflux disease. METHODS: Eighty-three patients with reflux disease and mild esophagitis were prospectively studied for the development of Barrett's metaplasia while receiving long-term therapy with proton pump inhibitors and cisapride. Only patients who had effective control of reflux symptoms and esophagitis were included. The surveillance time was 2 years. The outcome of these 83 patients was compared with that of 42 patients in whom antireflux surgery was performed with a median follow-up of 3.5 years. RESULTS: Twelve (14.5%) patients developed Barrett's while receiving medical therapy; this was not seen after surgery. Patients developing Barrett's had a weaker lower esophageal sphincter and peristalsis before treatment than patients with uncomplicated disease. CONCLUSIONS: Antireflux surgery is superior to medical therapy in the prevention of Barrett's metaplasia. Therefore, patients with reflux disease who have a weak lower esophageal sphincter and poor esophageal peristalsis should undergo antireflux surgery, even if they have only mild esophagitis. (+info)
Regional differences in the response of feline esophageal smooth muscle to stretch and cholinergic stimulation.
(74/633)
There are no objective differences in neural elements that explain regional differences in neural influences along the smooth muscle (SM) esophageal body (EB). Regional differences in muscle properties are present in the lower esophageal sphincter (LES). This study examines whether regional differences in SM properties exist along the EB and are reflected in length-tension relationships and responses to cholinergic excitation. Circular SM strips from feline EB at 1 cm (EB1) and 3 cm (EB3) above LES and from clasp and sling muscle bundles of LES were assessed in normal and calcium-free solutions with and without bethanechol stimulation. Neural inhibition was assessed by electrical field stimulation (EFS). EB3 developed significantly higher tension in response to stretch and to bethanechol than did EB1. The relaxation response to EFS in bethanechol-precontracted strips was less in EB3 than in EB1. In LES, clasp developed higher resting tension than sling but less active tension in response to bethanechol. EFS-induced relaxations of sling and clasp tissues precontracted by bethanechol were not different. In calcium-free solution, length-tension differences between EB3 and EB1 persisted, but those of LES clasp and sling were abolished. Therefore, regional myogenic differences exist in feline EB circular SM as well as in LES and may contribute to the nature of esophageal contraction. (+info)
Cytokeratin immunoreactivity of intestinal metaplasia at normal oesophagogastric junction indicates its aetiology.
(75/633)
BACKGROUND AND AIMS: Cytokeratin (CK) 7 and 20 patterns are specific for long and short segments of Barrett's oesophagus but their use has not been assessed in intestinal metaplasia arising in macroscopically normal gastro-oesophageal junction (GOJ). PATIENTS AND METHODS: This study was carried out in a large prospective series of 254 patients who underwent upper endoscopy, had normal gastro-oesophageal anatomy, and who had biopsies of the antrum, fundus, cardia, GOJ, and lower oesophagus. Intestinal metaplasia of the GOJ was typed by histochemistry with high iron diamine-alcian blue staining and by immunohistochemistry using CK7 and CK20 antibodies. Results were correlated with clinical, endoscopic, and pathological data. RESULTS: Sixty (23.6%) of our patients presenting with a normal GOJ had intestinal metaplasia. The CK7/CK20 pattern identified two groups of patients: one highly correlated with Barrett's and the other with characteristics of Helicobacter pylori gastritis. The Barrett's type CK7/CK20 pattern was related to a high frequency of gastro-oesophageal reflux symptoms (p<0.02) and normal endoscopic appearance of the stomach (p<0.03). In contrast, the gastric type CK7/CK20 pattern was linked to atrophic (p<0.02) or erythematous (p<0.05) appearance of the stomach (p<0.03), high frequency of H pylori infection (p<0.04), antral inflammation (p<0.006) with atrophy (p<0.02), and intestinal metaplasia (p<0.02). CONCLUSION: In patients presenting with intestinal metaplasia in normal appearing GOJ, the cytokeratin pattern identifies two groups of patients, one with features identical to those of long segment Barrett's oesophagus and one with features seen in H pylori gastritis. These data may be used by clinicians and should result in improved endoscopic surveillance strategies targeted specifically at patients at increased risk of Barrett's oesophagus and thus cancer. (+info)
Prolonged manometric recordings of oesophagus and lower oesophageal sphincter in achalasia patients.
(76/633)
BACKGROUND AND AIMS: Conventional short term manometry is a valuable tool in the diagnosis of achalasia but the technique may fail to detect intermittent motor events. The aim of this study was to investigate the pattern of lower oesophageal sphincter (LOS) and oesophageal pressures during prolonged recording in patients with achalasia. METHODS: Eleven patients with idiopathic achalasia were studied. Prolonged combined oesophageal pH and manometric recordings of the pharynx, LOS, and stomach were performed using a pH glass electrode and a multiple lumen assembly incorporating a Dent sleeve connected to a portable water perfused manometric system. RESULTS: LOS pressure varied during the day. Postprandial LOS pressures were lower than those recorded preprandially (1.2 v 1.8 kPa; p=0.005) and basal LOS pressures were significantly higher during phase III of the migrating motor complex than during the subsequent phase I (3.3 v 1.8 kPa; p=0.028). Complete LOS relaxations were occasionally observed in seven patients (0.48/h). Complete LOS relaxations were longer in duration than incomplete LOS relaxations (10.8 v 2.8 s; p=0.01) and 57% of complete relaxations fulfilled the criteria of a transient LOS relaxation (TLOSR). Complete LOS relaxations were associated with oesophageal pressure waves with higher amplitudes and longer durations. In addition, a higher proportion of these oesophageal pressure waves were spontaneous (55.6% v 0%; p<0.02) and multipeaked (72.7% v 0%). During prolonged manometry, high amplitude oesophageal pressure waves (>10 kPa) were recorded in six patients and retrograde oesophageal pressure waves in four, phenomena which were not observed during short term manometry. CONCLUSION: In contrast with short term stationary manometry, prolonged manometry in achalasia patients revealed the occurrence of complete LOS relaxations, TLOSRs, variations in LOS pressure associated with a meal or phase III, and high amplitude and retrograde oesophageal pressure waves. (+info)
Differences in calmodulin and calmodulin-binding proteins in phasic and tonic smooth muscles.
(77/633)
To determine whether densities of calmodulin (CaM) and CaM-binding proteins are related to phasic and tonic behavior of smooth muscles, we quantified these proteins in the opossum esophageal body (EB) and lower esophageal sphincter (LES), which represent phasic and tonic smooth muscles, respectively. Gel electrophoresis, immunoprecipitation, Western blot, and hemagglutinin epitope-tagged CaM (HA-CaM) overlay assay with quantitative scanning densitometry and phosphorylation measurements were used. Total protein content in the two smooth muscles was similar (approximately 30 mg protein/g frozen tissue). Total tissue concentration of CaM was significantly (25%) higher in EB than in LES (P < 0.05). HA-CaM-binding proteins were qualitatively similar in LES and EB extracts. Myosin, myristoylated alanine-rich C kinase substrate protein, Ca(2+)/CaM kinase II, and calponin contents were also similar in the two muscles. However, content and total activity of myosin light chain kinase (MLCK) and content of caldesmon (CaD) were three- to fourfold higher in EB than in LES. Increased CaM and MLCK content may allow for a wide range of contractile force varying from complete relaxation in the basal state to a large-amplitude, high-velocity contraction in EB phasic muscle. Increased content of CaD, which provides a braking mechanism on contraction, may further contribute to the phasic contractile behavior. In contrast, low CaM, MLCK, and CaD content may be responsible for a small range of contractile force seen in tonic muscle of LES. (+info)
Control of transient lower oesophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in patients with gastro-oesophageal reflux disease.
(78/633)
BACKGROUND AND AIMS: Transient lower oesophageal sphincter relaxations (TLOSRs) are the major cause of gastro-oesophageal reflux in normal subjects and in most patients with reflux disease. The gamma aminobutyric acid (GABA) receptor type B agonist, baclofen, is a potent inhibitor of TLOSRs in normal subjects. The aim of this study was to investigate the effect of baclofen on TLOSRs and postprandial gastro-oesophageal reflux in patients with reflux disease. METHODS: In 20 patients with reflux disease, oesophageal motility and pH were measured, with patients in the sitting position, for three hours after a 3000 kJ mixed nutrient meal. On separate days at least one week apart, 40 mg oral baclofen or placebo was given 90 minutes before the meal. RESULTS: Baclofen reduced the rate of TLOSRs by 40% from 15 (13.8-18.3) to 9 (5.8-13.3) per three hours (p<0.0002) and increased basal lower oesophageal sphincter pressure. Baclofen also significantly reduced the rate of reflux episodes by 43% from 7.0 (4.0-12.0) to 4.0 (1.5-9) per three hours (median (interquartile range); p<0.02). However, baclofen had no effect on oesophageal acid exposure (baclofen 4.9% (1.7-12.4) v placebo 5.0% (2.7-15.5)). CONCLUSIONS: In patients with reflux disease, the GABA(B) agonist baclofen significantly inhibits gastro-oesophageal reflux episodes by inhibition of TLOSRs. These findings suggest that GABA(B) agonists may be useful as therapeutic agents for the management of reflux disease. (+info)
Mechanical and electrophysiological effects of endothelin-1 on guinea-pig isolated lower oesophageal sphincter circular smooth muscle.
(79/633)
1. The effects of endothelin-1 (ET-1) on guinea-pig lower oesophageal sphincter (LOS) circular smooth muscle were investigated by using intracellular microelectrodes and isometric tension recording techniques. 2. ET-1 produced biphasic mechanical responses; an initial transient relaxation followed by a sustained contraction. The initial relaxation was not inhibited by either tetrodotoxin (TTX, 1 microM) or L-N(G)-nitroarginine (L-NOARG, 100 microM). The sustained contraction was greatly attenuated by nifedipine (1 microM). 3. ET-1 (1 - 30 nM) induced a concentration-dependent hyperpolarisation that was unaffected by TTX or L-NOARG. The ET(A) receptor antagonist, BQ123 (0.3 microM) abolished the ET-1-induced hyperpolarisation, whereas the ET(B) receptor antagonist, BQ788 (0.3 microM) had no detectable effect. Sarafotoxin S6c (10 nM) did not change the membrane potential. 4. The ET-1-induced hyperpolarisation was abolished by apamin (0.1 microM). Interestingly, apamin abolished the ET-1-induced transient relaxation but potentiated the sustained contraction. 5. In Ca(2+)-free Krebs solution, the ET-1-induced hyperpolarisation was greatly attenuated and returned to the control value when the tissue was reperfused with Krebs solution containing Ca(2+). The ET-1-induced hyperpolarisation was insensitive to nifedipine but was attenuated by SK&F 96365 (1 - [beta-[3-(4 - methoxy - phenyl)propoxy] - 4 - methoxyphenethyl] - 1H-imidazole hydrochloride, 50 microM), an inhibitor of receptor-mediated Ca(2+) entry. The residual component of the ET-1-induced hyperpolarisation was sensitive to thapsigargin (1 microM). 6. These results demonstrate that, in guinea-pig LOS circular smooth muscle, ET-1 hyperpolarizes the membrane by activating apamin-sensitive K(+) channels, mainly as a result of receptor-mediated Ca(2+) entry and partly by Ca(2+) release from intracellular stores. The hyperpolarisation triggers the initial transient relaxation, which acts to oppose the sustained contraction. (+info)
Intestinal metaplasia of the esophagus or esophagogastric junction: evidence of distinct clinical, pathologic, and histochemical staining features.
(80/633)
Our purpose was to evaluate the clinical, histologic, and histochemical staining characteristics of intestinal metaplasia (IM) at an endoscopically normal-appearing esophagogastric junction (IM-EGJ) compared with IM in a columnar-lined esophagus (IM-CLE). A prospective study included 253 patients referred for elective upper gastrointestinal endoscopy. Biopsy specimens were obtained from 2 cm above and immediately distal to the squamocolumnar junction, the gastric corpus, and the antrum. Any red mucosa above the EGJ was sampled. IM-CLE (prevalence, 5.5%) typically occurred in white male smokers with a long history of reflux symptoms. IM-EGJ (prevalence, 9.1%) was associated with corpus and antrum gastritis and with IM at these sites. IM-CLE usually (13/14 [93%]) was the incomplete type IM, whereas only 12 (52%) of 23 patients in the IM-EGJ group had incomplete IM. IM-EGJ and IM-CLE should be considered as separate entities. Further research is needed to evaluate whether neoplastic progression of IM-EGJ is related to its mucin profile. (+info)