Mechanisms underlying excessive esophageal acid exposure in patients with gastroesophageal reflux disease

The cause of reflux esophagitis (RE) is excessive esophageal acid exposure. Acid reflux and acid clearance after acid reflux are important factors related to excessive esophageal acid exposure. The main mechanism responsible for acid reflux is transient lower esophageal sphincter relaxation (TLESR), which is LES relaxation not associated with swallowing, and acid reflux caused by low LES pressure is rare. The frequency of TLESR in the postprandial period does not significantly differ between healthy subjects and gastroesophageal reflux disease (GERD) patients; however, the proportion of acid reflux episodes during TLESR is significantly higher in GERD patients. The layer of acid that appears above the dietary layer immediately below the esophagogastric junction (acid pocket) is attracting increasing attention as a cause of the difference in the proportion of acid reflux episodes during TLESR. The proportion of acid reflux episodes during TLESR is significantly higher when the acid pocket is present in the hernia sac than when it is located below the diaphragm. The acid pocket also shows upward migration and reaches the esophageal side of the esophagogastric junction, and the acid pocket itself has been suggested to cause mucosal damage in the lower esophagus. The amplitude and success rate of primary peristalsis decreases with increases in the severity of RE, leading to excessive esophageal acid exposure. Furthermore, the success rate of secondary peristalsis is lower in GERD patients than in healthy subjects.     

Excess gastroesophageal reflux in patients with hiatus hernia is caused by mechanisms other than transient LES relaxations

BACKGROUND & AIMS: Esophageal acid exposure is higher in gastroesophageal reflux disease (GERD) patients with hiatus hernia than in those without. We investigated the effect of a sliding hiatus hernia on the mechanisms underlying spontaneous gastroesophageal reflux over 24 hours. METHODS: Twelve GERD patients with and 10 GERD patients without hiatus hernia were studied for 24 hours. Combined esophageal pH and manometric recordings of the pharynx, lower esophageal sphincter (LES), and stomach were performed using a multiple-lumen assembly incorporating a Dent sleeve connected to a portable water-perfused manometric system and a pH glass electrode. RESULTS: Patients with hiatus hernia had greater esophageal acid exposure (7.6% vs. 3.3%; P < 0.01) and more reflux episodes (3.1 vs. 1.8/h; P < 0.001) than those without. LES pressure, the incidence of transient LES relaxations (TLESRs), and the proportion of TLESRs associated with acid reflux were comparable in both groups. Both groups had equal numbers of reflux episodes associated with TLESRs and swallow-associated prolonged LES relaxations. Patients with hiatus hernia had more reflux associated with low LES pressure, swallow-associated normal LES relaxations, and straining during periods with low LES pressure. CONCLUSIONS: The excess reflux in GERD patients with hiatus hernia compared with those without is caused by malfunction of the gastroesophageal barrier during low LES pressure, swallow-associated normal LES relaxations, deep inspiration, and straining.     

难治性胃食管反流病食管动力异常与反流特点的研究

目的研究难治性胃食管反流病(refractory gastroesophageal reflux disease,rGERD)食管动力学特征和反流特点。方法应用高分辨率食管测压(HRM)监测87例GERD患者和70例rGERD患者食管动力学数据,同时应用便携式24 h食管pH-阻抗监测仪记录两组患者的酸暴露特点、反流类型及反流特点,分析比较两组患者间差异。结果rGERD患者中UES压力、LES压力显著低于GERD患者(P<0.05),rGERD患者LES的长度与GERD患者比较,差异无统计学意义(P>0.05)。rGERD患者中食管动力障碍比例高于GERD患者(70.00%vs 33.33%,χ2=4.891,P<0.05),DCI下降为特征的食管蠕动收缩障碍及间断收缩为特征的食管收缩节律障碍者比例两组比较,差异无统计学意义(57.14%vs 62.07%;42.86%vs 37.93%,χ2=3.275、2.822,P>0.05)。rGERD患者DeMeester评分高于GERD患者(P=0.014),rGERD患者反流性质中弱酸反流及非酸反流明显多于GERD患者(P弱酸=0.001,P非酸=0.017),而酸反流次数差异无统计学意义(P酸=0.385);rGERD患者反流性状中气体反流及气液混合反流次数多于GERD患者(P气=0.022,P气液=0.031),而液体反流次数差异无统计学意义(P液=0.742)。结论rGERD患者与GERD患者相比,存在UES压力偏低、LES压力下降和食管蠕动收缩障碍等食管动力学异常;rGERD患者反流以弱酸反流及碱反流为主,而GERD患者以酸反流为主,同时rGERD患者中气液混合反流所占比例大,而GERD患者以液体反流为主。     

Effect of sodium valproate on esophageal motility in healthy subjects and patients with gastroesophageal reflux

BACKGROUND: There is experimental evidence to show that upper gastrointestinal tract motility is influenced by a GABAergic mechanism. Sodium valproate acts as a GABA agonist, and has been proven to affect the human internal anal sphincter. The aim of this study was to evaluate any possible effect of sodium valproate on esophageal motility in healthy subjects and patients with gastroesophageal reflux disease (GERD). METHODS: Ten healthy volunteers (4 M, 6 F; age range: 20-61 years) and 12 patients (4 M, 8 F; age range: 25-70 years) with GERD were included in the study. Standard esophageal manometry and ambulatory 24-h esophageal pH monitoring were performed before and 5 days after oral administration of sodium valproate (400 mg four times per day). Main measurements included a) lower esophageal sphincter (LES) resting pressure and amplitude and duration of peristalsis at 5, 10 and 15 cm proximal to LES, and b) percentage of time with esophageal pH <4 and number of reflux episodes. RESULTS: Sodium valproate (i) significantly increased LES resting pressure in both groups (P<0.05), without affecting either the LES postdeglutition relaxation or any of the parameters of the esophageal peristaltic activity, (ii) significantly reduced the number of reflux episodes at the postprandial period in both healthy subjects (P=0.02) and reflux patients without hiatal hernia (P=0.04) and (iii) the time percentage with esophageal pH <4 at the postprandial period in reflux patients (P=0.01). CONCLUSIONS: Sodium valproate increases normal and reduced tonic activity of the human LES and reduces the number of reflux episodes in health and GERD. This action could be attributed to a central GABAergic mechanism.     

下食管括约肌运动和功能与胃食管反流病

目的　观察胃食管反流病 (GERD)患者与对照组餐前、餐后食管pH情况 ,下食管括约肌(LES )运动模式的变化以及酸反流事件与一过性下食管括约肌松弛 (TLESR )、低LES压力 (LESP)的关系。方法　两组受试者均接受连续性 4h食管压力测定 (分别为空腹和餐后 1、2、3h)和食管pH监测 (GERD组检测 4h ,对照组检测 2 4h)。结果　GERD组酸反流事件明显高于对照组 (P <0 0 5 )。两组间TLESR发生率差异无显著性 (P >0 0 5 ) ,但与空腹比较 ,两组餐后 1h和 2hTLESR发生率明显增多 ;GERD组伴有酸反流的TLESR明显高于对照组 (P <0 0 0 1)。 4 3% (2 9/ 6 8)的酸反流事件发生在TLESR期间。 31% (2 1/ 6 8)的酸反流事件出现于低LESP状态中。结论　GERD是多因素参与的病理过程。LES运动形式变化和功能不全是GERD的重要背景因素。     

Gastric fullness, physical activity, and proximal extent of gastroesophageal reflux

OBJECTIVES: Proximal extent of gastroesophageal reflux (PER) is relevant for symptoms in GERD patients. It has been suggested that PER is determined by the volume of the refluxate that, in turn, might depend on the degree of gastric fullness. Abdominal straining, during ambulation, increases the likelihood of gastroesophageal reflux. We assessed the influence of gastric fullness and ambulation on proximal extent of reflux. METHODS: PER was assessed in 37 patients with GERD undergoing ambulatory pH impedance monitoring. In 14 controls and 19 GERD patients, esophageal pH impedance and gastric emptying were also studied simultaneously in stationary conditions. We compared PER during fasting, early postprandial (before half emptying), and late postprandial periods in ambulatory and stationary conditions. RESULTS: More reflux episodes reached the proximal esophagus in the postprandial period compared to fasting (60%+/-4 vs 29%+/-3, p<0.05). In stationary conditions, early postprandial reflux reached higher proximal extent than late postprandial reflux (15+/-3% vs 8+/-4%, p<0.05). The proportion of reflux events reaching the proximal esophagus was significantly higher in ambulatory than in stationary conditions (29+/-5% vs 15+/-3%, p<0.05). CONCLUSION: Compared to fasting, reflux episodes occurring after the meals are more likely to reach higher proximal extent, particularly so during the early postprandial period. The highest proportion of postprandial proximal reflux occurred in ambulatory condition. These findings suggest that reducing meal volumes and early postprandial physical activity might contribute to decrease proximal extent of reflux and postprandial GERD symptoms.     

Effect of laparoscopic partial fundoplication on reflux mechanisms

OBJECTIVES: Transient lower esophageal sphincter relaxations (TLESRs) are the main mechanism causing gastroesophageal reflux. Since 1994 we have performed laparoscopic partial instead of complete fundoplication as standard surgical treatment for therapy resistant reflux disease to minimize postoperative dysphagia. To better understand the management of gastroesophageal reflux, we conducted a prospective study of the effects of laparoscopic partial fundoplication on TLESRs and other reflux mechanisms. METHODS: From 1994 to 1999, 65 patients underwent laparoscopic partial fundoplication (180-200 degrees) and 28 of these patients (16 female, 12 male, mean age 43 +/- 2 yr [range, 26-66 yr]) agreed to participate in this prospective study on reflux mechanisms. Before and 6 months after surgery, all patients were evaluated by simultaneous recording of pH and lower esophageal sphincter characteristics, using sleeve manometry. RESULTS: After partial fundoplication basal LES pressure increased significantly (p < 0.05), from 14.3 +/- 1.2 mm Hg to 17.8 +/- 1 mm Hg. Partial fundoplication significantly (p < 0.05) decreased the number of TLESRs, from 3.4 +/- 0.8 to 1.6 +/- 0.3 per hour in the fasting period, and from 4.7 +/- 0.5 to 1.9 +/- 0.3 per hour postprandially. The percentage of TLESRs associated with reflux also decreased significantly (p < 0.05), from 45 +/- 7% to 27 +/- 6% after operation. The number of reflux episodes decreased significantly (p < 0.05), from 4.1 +/- 0.7 to 1.3 +/- 0.3 per hour postoperatively. The majority of these episodes were associated with TLESRs: 57% and 46%, pre- and postoperatively, respectively. CONCLUSIONS: Laparoscopic partial fundoplication significantly increased fasting and postprandial LES pressure and significantly decreased TLESR frequency. This resulted in a significant reduction in esophageal acid exposure, with preservation of postprandial LES characteristics.     

Endoscopic therapy for gastroesophageal reflux disease

Many new and developing endoscopic techniques for treatment of gastroesophageal reflux disease (GERD) are now or will soon be available for clinical use. These new therapies are directed to the gastroesophageal junction and include three basic techniques, which are outlined in this review: thermal remodeling and neurolysis of the lower esophageal sphincter (LES) zone; bulking or reinforcing of the LES; and plicating gastric folds at the gastric cardia. Only two of these treatments, radiofrequency ablation and fundic fold plication, have been approved by the US Food and Drug Administration (FDA). Published clinical research on endoscopic treatment is reviewed, although it is mostly comprised of open-label trials and anecdotal clinical reports. Complications of endoscopic GERD treatments are described as well as real and potential pitfalls of these techniques. Problems caused by premature introduction of endoscopic GERD treatments into the marketplace are also discussed, along with the rationale for FDA approval of similar devices.     

Intraesophageal pH monitoring after breakfast + lunch in gastroesophageal reflux

To evaluate intraesophageal pH monitoring during two consecutive 3-h postprandial periods (breakfast + lunch) in the diagnosis of pathological gastroesophageal reflux, we studied 40 patients with documented gastroesophageal reflux and 15 healthy controls. Reflux events were analyzed in the two separate postprandial periods, their sum (double postprandial pHmetry), and a standard 24-h period. Data from all pH-recording periods were compared and correlation coefficients were obtained between postprandial and 24-h reflux events. While pH recordings from the two separate postprandial periods provided good separation between patients and controls, double postprandial pHmetry was most accurate in the diagnosis of gastroesophageal reflux. In the latter procedure, mean percent reflux time was 2.5 +/- 1.8% in controls and 19.4% +/- 10.3% in patients (p less than 0.001), with a specificity of 100% and a sensitivity of 97%. A high degree of correlation existed for all reflux events between postprandial and 24-h pHmetries. We believe that double postprandial intraesophageal pH monitoring accurately distinguishes between normal persons and patients with pathological reflux. The technique considerably shortens the examination time in relation to 24-h pH monitoring and may prove the esophageal test of choice for objective evidence of gastroesophageal reflux.     

Gastric distention: a mechanism for postprandial gastroesophageal reflux

The occurrence of gastroesophageal reflux after meals may be related to an increase in the rate of transient lower esophageal sphincter (LES) relaxations, the mechanisms of which are not understood. We investigated the effects of gastric distention on LES pressure in 16 normal subjects and 17 patients with gastroesophageal reflux disease. Intraluminal pressure was measured in the gastric fundus, LES, and esophageal body with a manometric catheter incorporating a sleeve device. Gastric distention was performed by injecting 0, 250, 500, or 750 ml of air in randomized order into a balloon and maintaining each stimulus for 15 min. Gastric distention did not significantly alter resting LES pressure in either group. During the basal period the rate of transient LES relaxation in the reflux patients (1.1 +/- 0.4 per 15 min) was greater than that in the normal subjects (0.6 +/- 0.1 per 15 min). Gastric distention resulted in a significant threefold to fourfold increase in the rate of transient LES relaxations in both groups. The reflux patients had a significantly greater proportion of complete relaxations (87%) than did the normal subjects (73%). We conclude that gastric distention, by significantly increasing the rate of transient LES relaxations in both normal subjects and patients with gastroesophageal reflux disease, may contribute to the postprandial increase in gastroesophageal reflux.     

Composition of the postprandial refluxate in patients with gastroesophageal reflux disease

OBJECTIVE: It is not known whether the characteristics of the postprandial refluxate in patients with gastroesophageal reflux disease (GERD) differ from those observed in normal subjects. The aim of this study was to characterize the postprandial refluxate in adult patients with GERD using combined intraluminal electrical impedance and pH measurements. METHODS: Postprandial gastroesophageal reflux was assessed in 16 patients with GERD and 15 controls. pH and intraluminal electrical impedance were used to identify acid and nonacid reflux of liquid, mixed (liquid + gas) or gas. RESULTS: Transient lower esophageal sphincter relaxations (TLESRs) and reflux of gastric contents were equally frequent in both groups. However, patients with GERD had more acid reflux [8 (4.7-10.5)/h vs 3.5 (2.6-6)/h, p < 0.05], and normal subjects had more nonacid reflux [5 (4.3-6.7)/h is 3 (1-3.5)/h, p < 0.05]. Gas reflux was less frequent in GERD than in controls (51% vs 68%; p < 0.05). Pure liquid reflux, however, was more frequent (40% vs 26%, p < 0.05) and twice as likely to be acid in GERD. During TLESRs, liquid acid reflux was more frequent in GERD than in controls. CONCLUSIONS: TLESRs and reflux of gastric contents are similarly frequent in patients with GERD and controls. However, patients with GERD have more acid reflux and less nonacid reflux. Differences in the air-liquid composition of the refluxate may contribute to the higher rate of acid reflux observed in these patients.     

Comparison of esophageal acid exposure distribution along the esophagus among the different gastroesophageal reflux disease (GERD) groups

BACKGROUND: Patients with nonerosive reflux disease (NERD) have the lowest esophageal acid exposure profile compared with the other gastroesophageal reflux disease (GERD) groups. AIM: To compare lower esophageal acid exposure recordings 1 cm above the lower esophageal sphincter (LES) with those 6 cm above the LES as well as to determine the characteristics of esophageal acid exposure along the esophagus among the different GERD groups. METHODS: Patients with classic heartburn symptoms were enrolled into the study. Patients were evaluated by a demographics questionnaire and the validated GERD Symptom Checklist. Upper endoscopy was performed to evaluate the presence of esophageal erosions and Barrett's esophagus (BE). Ambulatory pH testing was performed using a commercially available 4-sensor pH probe with sensors located 5 cm apart. The distal sensor was placed 1 cm above the LES. RESULTS: Sixty-four patients completed the study. Of those, 21 patients had NERD, 20 had erosive esophagitis (EE), and 23 had BE. All patient groups demonstrated greater esophageal acid exposure 1 cm above the LES than 6 cm above the LES. In NERD and EE, this phenomenon was primarily a result of a higher mean percentage of upright time with pH <4. Unlike patients with EE and BE, those with NERD had very little variation in esophageal acid exposure throughout the esophagus (total and supine). CONCLUSIONS: ALL GERD groups demonstrated significant greater esophageal acid exposure at the very distal portion of the esophagus, primarily as a result of short upright reflux events. Unlike erosive esophagitis and BE, NERD patients demonstrate a more homogenous acid distribution along the esophagus.     

无效食管运动在胃食管反流病中发病作用的观察

目的　探讨食管无效收缩 (IEM)在胃食管反流病 (GERD)的发病作用。方法　对GERD病人行食管测压和 2 4h食管pH监测 ,分析IEM在GERD的发生率以及比较IEM与食管酸暴露、酸清除和食管炎的关系。结果　 86例GERD病人中 5 9例 (6 8 6 % )存在非特异性食管动力障碍 (NEMD) ;其中 5 5例 (占 93 2 % )符合IEM诊断标准 ;GERD病的IEM发生率为 6 3 95 %。IEM的GERD患者总的pH <4时间 (% ) (5 91)及立位 (4 4 3)和卧位 (6 92 )pH <4时间 (% )显著大于食管正常蠕动的GERD患者 (分别为 3 16 ,1.6 1,和 4 31) ,尤以卧位明显 (P <0 0 1)。IEM患者平均卧位食管酸清除时间 (EAC)为每次 12 6 3min ,显著长于正常食管动力GERD患者的每次 3 15min(P<0 0 1) ,而立位EAC则与正常食管动力组无差异。 2 7例正常食管动力GERD有 10例 (37% )有糜烂性食管炎 ;5 5例IEM患者有 19例 (35 % )有食管炎 ,二组间食管炎发生比例差异无显著性 (P >0 0 5 )。结论　GERD病的食管动力障碍大多数系IEM。IEM比正常食管动力患者更易发生反流和存在食管酸清除障碍。IEM是GERD病的主要异常表现。     

Upright versus supine reflux in gastroesophageal reflux disease

BACKGROUND: Postural measures are early recommendations in the management of heartburn, and are aimed at preventing acid reflux through an incompetent lower esophageal sphincter (LES). However, LES incompetence is found in only a minority of patients, and transient LES relaxations, primarily in the upright position, are currently recognized as the main pathophysiological abnormality in gastroesophageal reflux disease (GERD). We investigated the importance of supine acid reflux in patients with GERD. METHODS: Upon review of their clinical, manometric, pH monitoring and endoscopic characteristics, 85 patients with reflux symptoms were classified into three groups: Group A (n=22), consisting of symptomatic patients without esophagitis or pathological reflux; group B (n=38), symptomatic patients with reflux but no endoscopic esophagitis; and group C (n=25), symptomatic patients with both ulcerative or complicated esophagitis and pathological reflux. RESULTS: All groups were similar in age distribution. Groups B and C had a higher prevalence of hiatal hernia and reflux symptoms. Manometry revealed similar LES pressures in groups A and B, but lower LES pressure in group C (P < 0.005). In groups A and B, supine reflux, in terms of percentage of time with pH < 4, was less pronounced than upright reflux (P < 0.0001). In contrast, group C supine reflux was as pronounced as the upright reflux. CONCLUSIONS: The majority of patients reflux in the upright position. Only patients with complicated esophagitis have significant bipositional acid reflux. These findings suggest that unless the patient has severe reflux disease, postural measures may not be indicated.     

Endoluminal gastroplication for treatment of patients with classic gastroesophageal reflux symptoms and borderline 24-h pH studies

BACKGROUND: Patients with classic gastroesophageal reflux disease (GERD) symptoms and borderline 24-h pH studies are not considered to be good candidates for surgical fundoplication. Endoluminal gastroplication (ELGP) is a new endoscopic treatment for patients with GERD. The aim of this study was to evaluate the efficacy of ELGP in these patients. METHODS: Patients with heartburn, regurgitation symptoms and a DeMeester score of less than 30 were studied. ELGP involved placement of two or three plications within 2 cm of the gastroesophageal junction. Clinical outcomes measured were heartburn symptom score (HSS), regurgitation frequency score (RFS) and medication use. RESULTS: Twenty-five patients (11 M, 14 F, mean age of 51 years) had a medication use of 11.5 doses of proton-pump inhibitors per week prior to ELGP. Average lower esophageal sphincter pressure measured 15 +/- 8 mmHg, and average DeMeester score was 18 +/- 8. Nine patients had hiatal hernias and 11 had esophagitis. Twenty-four patients were available for a mean follow-up of 12 months. HSS significantly decreased from 48 to 17 (P < 0.01) and RFS was reduced from 1.8 to 0.7 (P < 0.01). Proton-pump inhibitor use was 5.3 doses per week (P < 0.01) post-ELGP; 12 patients (50%) were off medications, 3 (13%) had a 50% reduction in medication use, and in 9 (37%) there was no change. Complications were bleeding in one patient and aspiration pneumonia in another patient. CONCLUSIONS: Endoluminal gastroplication provides symptomatic relief for patients with classic GERD symptoms despite medical therapy and borderline 24-h pH studies.     

十二指肠胃食管反流在胃食管反流病中的作用

目的　研究十二指肠胃食管反流 (DGER)在胃食管反流病发病机制中的作用及其对非糜烂性反流病 (NERD)的诊断价值。方法　 95例患者根据内镜检查的结果分为反流性食管炎和NERD组 ,对其均进行 2 4h食管 pH和胆汁联合监测。 结果　反流性食管炎患者DGER的各项指标 :吸光度值 >0 14时间百分比 (% )、总反流次数和反流 >5min的次数分别为 19 0 5± 2 3 4 4、30 5 6±34 0 4和 5 90± 6 37,均显著高于NERD组相应的 7 2 6± 11 0 8、15 6 8± 2 0 92和 2 5 9± 3 5 7(P <0 0 5 ) ,而酸反流差异无显著性 ,随着反流性食管炎的程度加重DGER发生率增高 ;18 2 %的NERD患者存在单纯DGER ,联合胆汁监测可使NERD诊断阳性率由 6 5 9%升高到 84 1%。结论　DGER可以单独发生 ,在引起反流性食管黏膜损伤或症状方面都有作用 ,2 4h食管 pH和胆汁联合监测有助于NERD的诊断。     

The prevalence of gastroesophageal reflux in asthma patients without reflux symptoms

Gastroesophageal reflux is a potential trigger of asthma that may be clinically silent. This study examines the prevalence of gastroesophageal reflux in asthma patients without reflux symptoms. This prospective cohort study evaluated 26 patients with stable asthma without reflux symptoms using esophageal manometry and 24-h esophageal pH testing. Gastroesophageal reflux was considered present if esophageal acid contact times were abnormal. Demographic variables were analyzed to determine if they predicted the presence of gastroesophageal reflux. Asthma patients with asymptomatic gastroesophageal reflux were compared with 30 age-matched asthma patients with symptomatic gastroesophageal reflux. The prevalence of abnormal 24-h esophageal pH tests in asthma patients without reflux symptoms was 62% (16 of 26). Demographic variables did not predict abnormal 24-h esophageal pH tests in asthma patients with asymptomatic gastroesophageal reflux. Asthma patients with asymptomatic gastroesophageal reflux had higher amounts of proximal esophageal acid exposure (p < 0.05) compared with asthma patients with symptomatic gastroesophageal reflux. Because demographic variables do not predict abnormal 24-h esophageal pH tests in asthma patients without reflux symptoms, 24-h esophageal pH testing is required. This study suggests that gastroesophageal reflux is present in asthma patients, even in the absence of esophageal symptoms.     

The role of excessive esophageal acid exposure in patients with gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD), especially reflux esophagitis (RE), is characterized by excessive esophageal acid exposure. Transient lower esophageal sphincter (LES) relaxation is the major mechanism of acid reflux episodes in both healthy subjects (HS) and patients with GERD. In the sitting position, where acid reflux episodes often occur, there is no difference in the frequency of transient LES relaxations between these two groups; however, in patients with GERD, at 5 cm above the LES, the proportion of acid reflux episodes during transient LES relaxations is significantly greater than in the HS group. This difference is considered to be one of the causes of excessive esophageal acid exposure in patients with GERD, but its cause is still unclear. A recent study, which investigated the proportion of acid reflux episodes during transient LES relaxations at 2 and 7 cm above the LES, showed that there was no difference at 2 cm above the LES between HS and patients with RE, but at 7 cm they were significantly greater in patients with RE than in HS. Evaluation of acid reflux at 2 cm above the LES is difficult to measure, but the proximal extent of refluxate could be one of the important factors of excessive acid esophageal exposure in patients with RE. Ineffective esophageal motility, found in patients with moderate to severe RE, impairs esophageal bolus clearance of acid, therefore both the proximal extent of refluxate and the delay of esophageal bolus clearance of acid could be major causes of excessive esophageal acid exposure. Hiatus hernia also causes acid reflux, due to its association with hypotensive LES, and also impairs esophageal bolus clearance of acid.     

脂肪对胃食管酸反流的影响和体重指数与胃食管酸反流的关系

目的评估饮食脂肪对胃食管酸反流的影响和体重指数（BMI）与胃食管酸反流的关系。方法选择23例健康志愿者和22例胃食管反流病（GERD）患者,记录受试者基本情况,先行食管测压,先后两次服用低脂餐和高脂餐,每次监测餐后6h食管pH值。结果健康志愿者和GERD患者在两种热量相等的低脂餐和高脂餐后,pH〈4总反流时间百分率,反流时间〉5min的反流次数及总反流次数的比较,均无显著性差异（P〉0．05）;BMI≥25受试者的pH〈4总反流时间百分率和反流时间〉5min的反流次数高于BMI〈25受试者,两者有显著性差异（P〈0．01）。结论在同热量含量下,食物中脂肪含量对健康志愿者和GERD患者餐后6h酸反流无影响;而肥胖可能会增加胃食管酸反流。     

Acid and bile reflux in erosive reflux disease, non-erosive reflux disease and Barrett's esophagus

BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) may occur with acid, bile or in a mixed form. Endoscopic injury and mucosal metaplasia are a known sequlae to pathological GERD. The aim of the study was to determine the contribution of acid and duodenogastroesophageal reflux (DGER) to endoscopic severity in patients with GERD and Barrett's esophagus. METHODS: Ninety-one patients complaining of reflux symptoms were studied with upper gastrointestinal endoscopy and graded to non-erosive reflux disease (NERD), erosive reflux disease (ERD) and Barrett's esophagus (BE). Esophageal manometry and simultaneous ambulatory 24-h esophageal pH and bilirubin monitoring (Bilitec 2000) were done to all patients. RESULTS: Seventy one patients (78.0%) had ERD (Savary-Miller (grade I-III), 11 patients (12.1%) had NERD and 9 patients (9.9%) had BE suspected endoscopically and diagnosed by histological esophageal biopsy. Combined 24-h esophageal bilirubin and pH monitoring revealed that 39 patients (42.9%) had mixed acid and bile reflux, 16 (17.6%) had pathological acid reflux only, 18 (19.8%) had bile reflux only and 18 patients (19.8%) had no evidence of abnormal reflux. The percentage of the total time of bilirubin absorbance above 0.14, in 71 patients with ERD was (8.18 +/- 11.28%), and in 9 patients with BE was (15.48 +/- 30.48%) which was significantly greater than that in 11 patients with NERD (4.48 +/- 8.99%), p < 0.05 and p = 0.01 respectively. All BE patients had abnormal esophageal bile reflux (3 bile alone and 6 mixed bile and acid); 44 of 71 patients (61.97%) with ERD had abnormal esophageal bile reflux (13 bile alone and 31 mixed bile and acid); meanwhile 15 of them (21.2%) had abnormal acid exposure alone. Of the 11 patients with NERD, 4 patients (36.4%) had abnormal esophageal bile reflux, 2 of them mixed with acid. CONCLUSIONS: The Bilitec method reliably identifies the presence of bilirubin and quantitatively detects duodenogastroesophageal reflux of bile. Mixed reflux (acid and bile) is the chief pattern of reflux in GERD patients in this study. Bile reflux either alone or mixed with acid reflux contributes to the severity of erosive and non-erosive reflux disease as well as to Barrett's esophagus.