Relation between oesophageal acid exposure and healing of oesophagitis with omeprazole in patients with severe reflux oesophagitis.

BACKGROUND/AIMS--Reducing oesophageal acid exposure by suppressing acid secretion with omeprazole is highly effective in healing reflux oesophagitis. Some patients with severe oesophagitis, fail to heal and whether this results from inadequate acid suppression or other factors is unclear. The aim of this study, was to investigate the relation between oesophageal acid exposure and healing in patients with severe reflux oesophagitis treated with omeprazole. METHODS--Sixty one patients with grade 3 or 4 ulcerative oesophagitis were treated for eight weeks with omeprazole 20 mg every morning. Those patients unhealed at eight weeks were treated with 40 mg every morning for a further eight weeks. Endoscopy and 24 hour oesophageal pH monitoring were performed before treatment and at the end of each treatment phase while receiving treatment. RESULTS--Thirty per cent of patients failed to heal with the 20 mg dose. Unhealed patients had greater total 24 hour oesophageal acid exposure before treatment, and while receiving treatment also had greater acid exposure and a smaller reduction in acid exposure than did patients who healed. Forty seven per cent of the unhealed patients also failed to heal with the 40 mg dose. These patients had similar levels of acid exposure before treatment to those who healed, but had greater acid exposure while receiving treatment, particularly at night when supine. CONCLUSIONS--Patients with severe ulcerative oesophagitis who are refractory to omeprazole have greater oesophageal acid exposure while receiving treatment than responding patients. This is due to a reduced responsiveness to acid suppression, and is likely to be an important factor underlying the failure of the oesophagitis to heal.     

Oesophageal motor events at the occurrence of acid reflux and during endogenous acid exposure in healthy subjects and in patients with oesophagitis.

In order to assess the oesophageal motor events associated with the occurrence of gastro-oesophageal acid reflux and those during endogenous acid exposure, we studied six healthy subjects and nine patients with symptoms and lesions of reflux oesophagitis. In the case of each subject simultaneous pressure and pH measurements of the distal oesophagus were taken both in fasting conditions and after a standardised balanced meal. Reflux episodes occurred in the absence of a lower oesophageal sphincter relaxation (34.3%, 17.7%) or in the presence of a relaxation associated (34.2%, 30.8%) or unassociated (31.5%, 51.5%) with a peristaltic sequence, in the controls and patients respectively. No significant differences were found between the two groups. During endogenous acid perfusion the distal oesophagus showed mainly a peristaltic motor activity, but the mean hourly number of peristaltic sequences was significantly lower in the patients than in the controls (33.5 +/- 27.2 vs 81.5 +/- 3.2, p less than 0.01). Our results show that the mechanisms of reflux are similar in controls and in patients, while the peristaltic frequency is reduced in the latter. This motor failure may be responsible for the increased reflux duration observed in patients with oesophagitis.     

Salivary response to esophageal acid in normal subjects and patients with reflux esophagitis

We studied the effect of esophageal acid perfusion on salivation in patients with reflux esophagitis and in normal subjects. Serial 10-min saliva collections were obtained by expectoration during perfusion of the esophagus with water, and then 0.1 N HCl (pH 1.2) for 50 min or 0.01 N HCl (pH 2.1) for 120 min. Within 1-5 min of beginning 0.1 N HCl perfusion, all 8 patients with esophagitis developed heartburn accompanied by an increase in saliva flow. By the time the severity of heartburn required discontinuation of HCl perfusion (10-40 min), saliva flow had increased nearly fourfold. With 0.1 N HCl perfusion, 8 of 10 volunteers developed mild heartburn after 22 +/- 3 min (mean +/- SE), whereas 0.01 N HCl induced heartburn in 6 of 10 volunteers after 57 +/- 12 min of perfusion. Saliva flow increased concurrently with the onset of heartburn and doubled in those volunteers who developed heartburn. Saliva flow did not change in those volunteers who were without heartburn. We conclude that esophageal acid perfusion unaccompanied by heartburn does not affect salivation. However, saliva flow increases concurrently with the onset of heartburn, a phenomenon called "water brash" when clinically evident. The increased saliva flow that accompanies heartburn may act as an endogenous antacid that serves as a protective response to symptomatic gastroesophageal reflux.     

Patterns of acid reflux in complicated oesophagitis.

Oesophageal manometry and 24 hour ambulatory pH recordings from the distal oesophagus were carried out in 25 patients with complications of oesophagitis (stricture, Barrett's oesophagus or oesophageal ulcer) and compared with 25 patients with uncomplicated oesophagitis. Acid reflux was more severe in the complicated group with 26.2% of time below pH 4 compared with 11.3% in uncomplicated patients (p less than 0.01). This difference was most marked at night, when complicated patients had long periods of acid reflux with 35.6% time less than pH 4 compared with 5.2% uncomplicated (p less than 0.001). The mean duration of nocturnal acid reflux was 15.4 minutes (2.1 minutes uncomplicated, p less than 0.001). Oesophageal motility was markedly abnormal in all groups, but with no demonstrable differences in lower oesophageal sphincter pressure or peristalsis between the groups. Patients with complications of oesophagitis have different patterns of acid reflux from uncomplicated patients, with prolonged nocturnal bathing of the oesophageal mucosa, which may be the cause of stricture formation, metaplasia, or ulceration.     

Gastro-oesophageal acid reflux and sphincter pressure in normal human subjects.

Twelve-hour continuous recording of pH at the distal end of the oesophagus and manometric study of the basal gastro-oesophageal sphincter pressure were carried out in 26 normal human subjects. Eighteen of the 26 had 1-33 reflux episodes. The duration of each episode was shorter than 15 min in 16 of these 18 subjects. One single reflux episode lasting 15-30 min occurred in two, and one lasting 30-45 min was recorded in one. The total duration of low pH is expressed in percentages of the total time of recording and is dependent on the criteria used for low pH. On automatic analysis of the course of investigation, pH below 2.3 was found in five, pH below 3 in 17, and pH below 4 and 5, in 18 of the 26 subjects. Basal gastro-oesophageal sphincter pressure flutuated between 8 and 24 mmHg. The results of the study would suggest that in healthy, asymptomatic individuals the gastro-oesophageal barrier against reflux may be periodically incompetent. If contact between acid gastric contents and the oesophageal mucosa is a factor provoking the symptom heartburn, low oesophageal pH need not necessarily give rise to symptoms, i.e. the sensibility to low pH is either individual, or patients with symptoms have considerably more frequent and longer lasting episodes of reflux with low oesophageal pH than have normal subjects.     

Enterogastric reflux in normal subjects and patients with Bilroth II gastroenterostomy. Measurement of enterogastric reflux.

Initially, scintigraphy was established as a valid method for detecting and quantitating enterogastric reflux. A new, tubeless technique for the measurement of enterogastric reflux was developed. 99mTc bound to [(2,6 dimethylphenylcarbamoylmethyl) iminodiacetic acid] (5 mCi) was administered intravenously to visualize the liver and biliary tract. One hour later, a standard liquid meal labeled with 111In bound to diethylene-triamine penta-acetic acid (250 microCi) was given. The 99mTc and 111In activities were recorded simultaneously for 1-min periods at 15-min intervals for 2 hr over liver, gallbladder, and gastric areas of interest. Enterogastric reflux indices were determined. Ten normal subjects and 13 patients with vagotomy, hemigastrectomy, and Bilroth II gastrojejunostomy were evaluated. The enterogastric reflux index in asymptomatic postsurgical patients was increased significantly to 24.6 +/- 4.7 compared with 8.2 +/- 6.0 (P less than 0.01) in normal subjects. In postsurgical patients with the syndrome of alkaline gastritis, the enterogastric reflux index was increased significantly to 86.3 +/- 7.1 (P less than 0.01) compared with asymptomatic postsurgical patients.     

胃食管反流患者夜间酸突破与食管酸暴露及幽门螺杆菌感染的临床研究

目的 探讨胃食管反流病(GERD)患者夜间酸突破(NAB)与食管酸暴露及幽门螺杆菌(Hp)感染的关系及临床意义.方法 GERD患者随机分为两组,每组26例,每组给予埃索美拉唑20 mg,每日2次,其中1组睡前加服雷尼替丁150 mg,疗程1周.两组治疗前后行24 h食管pH检测及食管症状评分并进行比较.结果 埃索美拉唑组,加服雷尼替丁组治疗后夜间胃pH小于4.0的时间百分比分别为37%、15%,显著低于治疗前90%、90%,后者夜间胃pH小于4.0的中位时间百分比显著低于前者(P＜0.05).加服雷尼替丁组NAB发生率为15.1%,埃索美拉唑组为34.5%,两组比较有统计学意义(P＜0.05),两组治疗前后夜间食管pH小于4的中位时间百分比差异无统计学意义(P＞0.05),其症状积分比较差异有统计学意义(P＜0.05).合计34例Hp阳性中有7例(20.5%)发生NAB,而18例Hp阴性者中10例出现NAB(55.6%,P＜0.05).结论 在胃食管反流中,中国人NAB发生率较低,食管酸抑制和症状控制不依赖于NAB的消除程度,NAB与Hp感染密切相关.     

Predominant nocturnal acid reflux in patients with Los Angeles grade C and D reflux esophagitis

BACKGROUND AND AIMS: Nocturnal gastric acid breakthrough (NAB) is defined as an intragastric pH < 4.0 lasting more than 1 h during the night in patients taking a proton pump inhibitor (PPI). Gastroesophageal reflux disease (GERD) patients with nocturnal gastroesophageal acid reflux accompanied by NAB are thought to be refractory to PPI treatment. The aim of this study was to endoscopically identify the patients with predominant nocturnal gastroesophageal acid reflux. METHODS: The subjects were 37 patients with erosive reflux esophagitis (Los Angeles classification (LA) grade A, 12; B, 10; C, eight; and D, seven cases) and a control group of 20 patients without esophagitis. The results of ambulatory 24 h gastric and esophageal pH monitoring were compared among different grades of esophagitis. RESULTS: Gastroesophageal reflux during 24 h in patients with high-grade esophagitis was more frequent than for patients with low-grade esophagitis or no esophagitis. Although the length of esophageal acid exposure (percentage time with pH < 4.0) in patients with grade A or without esophagitis was longer in the daytime, that in patients with grades C and D was longer during the night. The reason for the delayed nocturnal acid exposure was the longer nocturnal acid clearance in high-grade reflux esophagitis. CONCLUSIONS: Nocturnal exposure of the esophagus to acid occurs frequently in patients with LA grades C and D esophagitis. Thus, the existence of NAB with resulting nocturnal acid reflux should be considered when the patient with high-grade esophagitis shows resistance to PPI treatment.     

Eradication of Helicobacter pylori does not increase acid reflux in patients with mild to moderate reflux oesophagitis

BACKGROUND: A substantial minority of patients with gastro-oesophageal reflux disease (GERD) are infected with Helicobacter pylori, but there is controversy as to whether these patients should be treated for their infection. We hypothesized that H. pylori eradication increases gastro-oesophageal acid reflux in such patients with time. METHODS: Thirty-five consecutive H. pylori-infected patients (16 M and 19 F) with mild or moderate reflux oesophagitis were enrolled. Twenty-four-hour intra-oesophageal (n = 35) and intragastric (n = 12) pH-metry was recorded before and 15 months after H. pylori eradication. Gastric biopsy specimens from the antrum and corpus were obtained from 10 consecutive patients before and 15 months after H. pylori eradication. RESULTS: Fifteen months after eradication of H. pylori there was a significant decrease in percentage time oesophageal pH < 4 in the recumbent position only (P = 0.04). Despite a marked reduction in the severity of gastritis, there was no significant change in gastric acidity, total intra-oesophageal acid exposure or symptom score. Heartburn improved in 12, worsened in 7. and remained unchanged in 16 patients (P = 0.36) without any significant relationship to individual changes in acid exposure (P = 0.60). CONCLUSIONS: H. pylori eradication does not increase gastric acidity or gastro-oesophageal acid reflux in patients with mild to moderate reflux oesophagitis over the first 15 months.     

Alkaline reflux oesophagitis.

Duodenal and gastric contents do reflux into the oesophagus and acid alone certainly causes oesophageal damage which will be worsened by pepsin. In the patient who has undergone gastrectomy duodenal secretions may also be harmful. There is evidence that when the two mix there may be a toxic synergism, leading to mucosal disruption and intracellular damage to oesophageal cells which produces the clinical picture of reflux oesophagitis, with or without symptoms. Clear evidence of the toxicity of duodenal refluxate in humans is lacking, but the ability to measure bile and acid reflux continuously, together with a method of detecting oesophageal damage at a cellular level should help to solve this long debated problem.     

Acid gastro-oesophageal reflux and oesophageal pressure activity during postprandial and nocturnal periods. A study in subjects with and without pathologic acid gastro-oesophageal reflux

The aim of the investigation was to evaluate the relative quantity of acid gastrooesophageal reflux during different time periods in subjects with and without pathologic reflux. Twenty duodenal ulcer patients, 10 with and 10 without pathologic acid gastro-oesophageal reflux, and 26 asymptomatic volunteers were subjected to 12 h of simultaneous monitoring of pH and pressure activity in the oesophagus. The monitoring period was divided into a 3-h postprandial period, a night period of 6 h, and a 3-h period in the morning. The highest reflux frequency and the longest duration of oesophageal acid exposure were found in the postprandial hours (p less than 0.001). Thereafter, all groups had an even reduction in reflux rate. A greater absolute reduction in the duration of oesophageal acid exposure could be measured in patients with pathologic reflux as compared with the other groups (p less than 0.001). In spite of this, both reflux frequency and time with acid in the oesophagus were increased during the night in patients with pathologic reflux (p less than 0.001). Pathologic refluxers had in total 11 times as much reflux as normal subjects, and in addition 37.9% of the reflux took place during the 6 night hours. In contrast, only 5.4% of the reflux recorded in normal subjects occurred during this period. The pressure activity during periods with a normal intraoesophageal pH was reduced in all three groups during the night (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of reflux oesophagitis with ranitidine.

The efficacy of ranitidine was evaluated using a two-staged trial in patients with endoscopically moderate or severe reflux oesophagitis. The results of a six week double blind placebo controlled trial (stage I) in 36 patients shows that ranitidine (150 mg bd) is superior to placebo in the acute treatment with significant symptomatic improvement concerning heartburn and regurgitation, and in healing or improvement of endoscopic lesions. Prolonged treatment with ranitidine for another six weeks (stage II) proved to be effective in more resistant cases. No clinical side effects or significant biochemical changes were noted during this trial.     

Effect of hyoscine N-butylbromide on gastroesophageal reflux in normal subjects and patients with gastroesophageal reflux disease

OBJECTIVES: Recent studies have shown that atropine reduces gastroesophageal reflux in normal subjects and patients with gastroesophageal reflux. The aim of the study has been to assess the effects of an atropine derivative, hyoscine N-butylbromide in normal subjects and patients with gastroesophageal reflux disease by recording esophageal and gastric pH-metry for a 24-h period. METHODS: Ten normal subjects and 10 patients with gastroesophageal reflux disease were evaluated. PH-metry was performed using two glass pH flexible probes with distal incorporated electrodes. The two catheters were introduced nasally under fluoroscopy. One probe was positioned in the gastric body; the other was placed 5 cm above the lower esophageal sphincter which had been evaluated manometrically before the study. Recording lasted without interruption for 48 h. Patients and normal subjects were assigned to receive hyoscine N-butylbromide (10 mg p.o. t.i.d.) for 24 h followed by a placebo for another 24 h or vice versa in a random manner. The pH was analyzed for a total number of acid refluxes and percentage of the period with pH <4 in the esophagus and the mean gastric pH in 24 h, before and after treatment with hyoscine N-butylbromide. RESULTS: The number of reflux episodes was significantly greater with hyoscine N-butylbromide in comparison with a placebo in patients with gastroesophageal reflux disease and normal subjects (p < 0.02). The percentage of time with pH <4, was also significantly greater in patients with gastroesophageal reflux disease and in controls (p < 0.05). The mean 24-h gastric pH after hyoscine N-butylbromide was not different from placebo in gastroesophageal reflux disease and controls. CONCLUSIONS: Hyoscine N-butylbromide, an anticholinergic agent, increases the total number of esophageal acid refluxes in patients with gastroesophageal reflux disease and in controls, therefore it is not recommended in the treatment of gastroesophageal reflux disease.     

Alkaline intra-oesophageal pH and gastro-oesophageal reflux in patients with peptic oesophagitis

Simultaneous 22-h measurements of intra-oesophageal and intragastric pH were made in 22 patients with symptoms of gastro-oesophageal reflux (7 with peptic oesophagitis, 8 with peptic oesophageal stricture, and 7 with peptic oesophagitis and previous partial gastrectomy) to determine whether alkaline intra-oesophageal pH is a consequence of alkaline gastro-oesophageal reflux. In the three groups of patients intra-oesophageal pH was greater than 7 for 16.9 +/- 4.8%, 27.5 +/- 7.6%, and 21.0 +/- 7.7%, respectively, of total recording time (p = NS). Intragastric pH greater than 7 was recorded only in the patients with partial gastrectomy (10.3 +/- 5.3% of recording time; p less than 0.01 in comparison with the other groups). Elevations of intra-oesophageal pH to greater than 7 never occurred during episodes of alkalinization of intragastric pH. These results suggest that refluxed fluids are unlikely to be the cause of alkaline intra-oesophageal pH in patients with peptic oesophagitis.     

CT findings in a child with reflux oesophagitis.

We report the case of a 7-month-old boy who presented with a history of vomiting since birth. A computed tomography study showed circumferential thickening of the lower oesophageal wall with enhancement of the mucosa. After a period of antireflux medication, the patient underwent simultaneous oesophageal dilatation and Nissen fundoplication. He is doing well at 2-year follow up.     

Bile reflux and oesophagitis

Duodenal contents, and especially bile acids and trypsin, are noxious to the oesophageal mucosa, their damaging potential depending on pH. Various methodologies have been used to measure duodenogastric or duodenogastro-oesophageal reflux, all of them having technical limitations. Controversy exists as to the extent of duodenogastric reflux in GORD. Reflux of both acid and duodenal contents into the oesophagus increases with worsening of oesophagitis. Experimental data suggest that bile acids and trypsin are noxious to the oesophageal mucosa and that their damaging potential depends on pH. The injurious concentrations are, however, higher than those usually observed in the human oesophagus. Direct measurement of bile acids and trypsin is difficult and various methodologies have been used to measure duodenogastric or duodenogastro-oesophageal reflux, all of them having technical limitations. Whereas available data as to the extent of duodenogastric reflux in gastro-oesophageal reflux disease (GORD) are controversial, most observations show that reflux of both acid and duodenal contents into the oesophagus increases with worsening of oesophagitis. Furthermore, acid and duodenal contents occur simultaneously in most reflux episodes. In this issue of the journal, Marshall et al. report that exposure of the gastric fundus to duodenal contents as assessed by bilirubin monitoring is similar in GORD patients with varying degrees of oesophageal mucosal injury and in healthy controls.     

Cisapride: influence on oesophageal and gastric emptying and gastro-oesophageal reflux in patients with reflux oesophagitis

A preliminary, double-blind placebo controlled trial of cisapride in reflux oesophagitis was conducted. Eighteen patients were allocated to treatment with either placebo or cisapride, 10 mg three times daily, orally, before meals. Gastric emptying of a scrambled egg meal, oesophageal transit of a liquid bolus and ambulatory monitoring of oesophageal pH were assessed before and after four weeks' therapy. Overall, gastric emptying rates were not influenced by cisapride, although a small but significant reduction in gastric isotope retention, 20 minutes after meal ingestion was observed in patients on the active drug. Oesophageal transit times were not altered by cisapride. A small but significant reduction in the duration of gastro-oesophageal reflux followed cisapride therapy when compared with placebo.