Comparison of omeprazole and ranitidine in treatment of refractory gastroesophageal reflux disease in patients with gastric acid hypersecretion

Secretion of gastric acid and volume, serum gastrin concentration, and ambulatory 24-hr esophageal pH monitoring were evaluated prospectively in 12 patients with idiopathic gastric acid hypersecretion (basal acid output greater than 10.0 meq/hr) undergoing treatment for refractory chronic long-standing pyrosis. Treatment lasted six months and consisted of three months of ranitidine (mean 2150 mg/day, range 1200–3000 mg/day), followed by three months of omeprazole (mean 33 mg/day, range 20–60 mg/day). Both ranitidine and omeprazole significantly reduced gastric acid output (P<0.001) and gastric volume output (P<0.001) compared to a basal evaluation and resulted in complete disappearance of pyrosis. Total reflux time (percent 24 hr intraesophageal pH less than 4) was significantly reduced by ranitidine (P<0.02) and omeprazole (P<0.001) compared to basal evaluation; however, the effects of omeprazole were significantly greater than ranitidine (P<0.05). Omeprazole caused a significant increase in serum gastrin concentration compared to both basal and ranitidine (P<0.05). Endoscopically documented erosive esophagitis was present in nine of the 12 patients, and seven of the 12 patients had Barrett's epithelium. All 12 patients had complete resolution of pyrosis and healed esophagitis by six months, but no significant endoscopic regression was observed in the extent of Barrett's epithelium. No side effects occurred with these high doses of ranitidine or omeprazole. These results indicate that high-dose ranitidine and omeprazole are effective therapy for refractory gastroesophageal reflux disease. However, with omeprazole, total reflux times are reduced more than with ranitidine, often into the normal range. That marked reduction of gastric acid secretion with omeprazole, which greatly reduces total reflux times, accounts for the significant elevation of serum gastrin concentration seen during omeprazole therapy.     

Ranitidine therapy in patients with idiopathic gastric acid hypersecretion

One hundred twenty-four patients with idiopathic gastric acid hypersecretion (basal acid output greater than 10.0 meq/hr) were prospectively evaluated and treated with ranitidine twice a day. Fifty-four patients (44%) required standard doses of ranitidine 300 mg/day for adequate treatment, and the other 70 patients (56%) required increased doses of ranitidine (mean 994 mg/day, range 600–3000 mg/day). Mean basal acid outputs for these two groups were 14.0 and 16.6 meq/hr, respectively, which were not significantly different. Nevertheless, there was a significant correlation between basal acid output and daily ranitidine dose required for therapy (r=0.18,P=0.05). The duration of ranitidine therapy consisted of: <1 year (N=46), 1 year (N=16), 2 years (N=19), 3 years (N=22), 4 years (N=15), 5 years (N=6). Only five patients required progressive increases in ranitidine during the time of treatment, which consisted of an average of 0.5 dose adjustments per year. No side effects occurred with any of these high doses of ranitidine. These results indicate that, as in Zollinger-Ellison syndrome, ranitidine is effective therapy for patients with idiopathic gastric acid hypersecretion; however, markedly increased doses as large as 3000 mg/day may be required.     

Postprandial proximal gastric acid pocket and gastroesophageal reflux disease

An unbuffered layer of acidity that escapes neutralization by food has been demonstrated in volunteers and gastroesophageal reflux disease patients. This postprandial proximal gastric acid pocket (PPGAP) is manometrically defined by the presence of acid reading (pH < 4) in a segment of the proximal stomach between nonacid segments distally (food) and proximally (lower esophageal sphincter or distal esophagus). The PPGAP may have important clinical implications; however, it is still poorly understood. Gastric anatomy and physiology seem to be important elements for PPGAP genesis. Gastric operations and acid suppression medications may decrease distal – proximal intragastric acid reflux and help control gastroesophageal reflux.     

Evaluation of gastric emptying by electrogastrography and ultrasonography in gastroesophageal reflux disease

Background: It has been suggested that transient lower esophageal sphincter relaxation is involved in the occurrence of gastroesophageal reflux disease (GERD) and that decreased gastric emptying is an exacerbating factor of transient LES relaxation. In addition, the gastric emptying function is considered to be closely related to gastric motility. Methods: Gastric activity was evaluated by electrogastrography (EGG) in 22 patients with endoscopically positive reflux esophagitis (15 with mild esophagitis of Los Angeles grade A or B and seven with severe esophagitis of Los Angeles grade C or D) and 20 normal individuals. The gastric emptying function was also evaluated by abdominal ultrasonography. The sampling cycle of EGG was 1 s, and the measured frequency was 2.1–6.0 cycle/min (c.p.m.). The mean amplitude of EGG was compared by EGG spectral analysis among brady‐gastria cases with a contraction frequency of less than 2.4 c.p.m., normo‐gastria cases with a contraction frequency of 2.4–3.6 c.p.m., and tachy‐gastria cases with a contraction frequency exceeding 3.6 c.p.m. Results: In the patients with GERD, both the frequency of 3‐c.p.m. waves and peak frequency were reduced, and the gastric emptying function examined by ultrasonography had deteriorated, in comparison with normal individuals. Of those with GERD, the ultrasonographic gastric emptying function was significantly reduced in all patients with severe esophagitis compared with those with mild esophagitis, but the differences of the frequency of 3‐c.p.m. waves, the peak frequency, were not significant. Also, no significant difference was observed in the frequency of 3‐c.p.m. waves or the ultrasonographic gastric emptying function between the 16 patients with hiatal hernia and the six patients with no hiatal hernia. However, the mean amplitude in brady‐gastria and tachy‐gastria was significantly increased in the patients with hiatal hernia compared to those without hiatal hernia. Conclusions: Reduced gastric motility was suggested to be involved in the development of reflux esophagitis, and the presence of hiatal hernia was considered to have some effect on gastric motility.     

Idiopathic gastric acid hypersecretion

Many patients with acid-peptic disease have idiopathic gastric acid hypersecretion defined as a basal acid output >10.0 meq/hr; however, a significant proportion have basal acid outputs >15.0 meq/hr, which is within the range found in Zollinger-Ellison syndrome. Although idiopathic gastric acid hypersecretion is more common than Zollinger-Ellison syndrome, it is important that these two disorders be differentiated because of differences in treatment and natural history. In the present study, we compared 124 patients with idiopathic gastric acid hypersecretion and 137 patients with Zollinger-Ellison syndrome. There were no significant differences with regard to age at diagnosis, history of upper gastrointestinal hemorrhage, nausea, vomiting, and family history of duodenal ulcer and other acid-peptic disease. However, significant differences were observed between patients with idiopathic gastric acid hypersecretion and patients with Zollinger-Ellison syndrome with regard to percentage of males: 77% compared to 64% (P=0.008), mean serum gastrin: 60 pg/ml compared to 3679 pg/ml (normal <100 pg/ml) (P<0.001), mean basal acid output: 15.4 meq/hr compared to 47.0 meq/hr (P<0.001), mean age at onset of symptoms: 33 years compared to 41 years (P<0.001), mean duration of symptoms before diagnosis: 11 years compared to five years (P<0.001), percentage with abdominal pain: 67% compared to 82% (P=0.00004), percentage with diarrhea: 12% compared to 75% (P<0.000001), percentage with pyrosis: 58% compared to 40% (P=0.003), percentage with duodenal ulcer: 53% compared to 74% (P<0.000001), and percentage with esophagitis: 31% compared to 42% (P=0.0004). The differences in clinical features could be attributed to difference in mean basal acid output, and/or differences in levels of basal acid output used for diagnosis of idiopathic gastric acid hypersecretion (basal acid output >10.0 meq/hr) and Zollinger-Ellison syndrome (basal acid output >15.0 meq/hr). When 45 patients with idiopathic gastric acid hypersecretion and 39 patients with Zollinger-Ellison syndrome with basal acid outputs 15.1–30.0 meq/hr were compared, the main significant differences were with regard to mean serum gastrin: 69 pg/ml compared to 655 pg/ml (P<0.001), percentage of male gender: 82% compared to 62% (P=0.03), and percentage with diarrhea: 16% compared to 64% (P=0.000005). These results indicate that in general patients with idiopathic gastric acid hypersecretion and patients with Zollinger-Ellison syndrome often have similar clinical features that can be difficult to distinguish. However, the increased frequency of diarrhea and female gender should lead to a strong suspicion of Zollinger-Ellison syndrome, which can be distinguished in almost every case by measurement of serum gastrin.     

Relationship between acceleration of gastric emptying and oesophageal acid exposure in patients with endoscopy-negative gastro-oesophageal reflux disease

Objective. A delay in gastric emptying has been reported in patients with gastro-oesophageal reflux disease (GORD), but its role in increasing the number of reflux episodes is still debated. The aim of this study was to assess the relationship between acceleration of gastric emptying and gastro-oesophageal reflux in patients with endoscopy-negative GORD and pathological oesophageal acid exposure. Material and methods. Twelve patients (7 M, age range 24–65 years) underwent 6-h postprandial (2.1 MJ meal) combined gastric emptying by real-time ultrasonography and intra-oesophageal pH monitoring after cisapride (20 mg b.i.d.) and placebo for 3 days, on two separate occasions at least 7 days apart in double-blind randomized order. Gastric emptying after placebo was also measured in 12 healthy volunteers (7 M, age range 25–54 years). Results. In the patients’ group, the area under the emptying time curve was greater (p<0.01), and half and total emptying times prolonged (p<0.01) compared to the healthy subjects, 115 min (mean)±6 (SEM) versus 86±6 and 232 min±16 versus 160±7, respectively. Cisapride accelerated both half- and total gastric emptying (p<0.02): ?22 min (mean); ?10 to ?34 (95% CI) and ?48 min; ?10 to ?85, respectively, decreased both percentage of time at pH?p<0.01) and number of reflux episodes (p<0.05). However, no relationship was found between changes in gastric emptying and in the reflux variables by linear regression analysis (R²<0.005). Conclusion. The emptying rate of the whole stomach is not a major determinant of gastro-oesophageal reflux.     

Prevalence of gastroesophageal reflux disease and gastroesophageal reflux disease symptoms in Japan

BACKGROUND AND AIM: Epidemiological studies have shown that 10-48% of people in developed countries have gastroesophageal reflux disease (GERD) symptoms such as heartburn and acid regurgitation. The present study aimed to examine the prevalence of GERD symptoms and GERD in Japanese subjects. METHODS: A cross-sectional study of Japanese subjects who visited a clinic for a routine health check up was carried out. Subjects were asked to fill out a self-report questionnaire. GERD was defined as the presence of heartburn and/or acid regurgitation at least twice per week. RESULTS: Of the 6035 eligible subjects, 2662 (44.1%) reported having had heartburn and/or acid regurgitation during the past year: 124 (2.1%) daily, 275 (4.6%) twice per week, 773 (12.8%) twice per month and 1490 (24.7%) less than twice per month. Three hundred and ninety-nine (6.6%) subjects were diagnosed as having GERD and there was no relationship between the prevalence of GERD and either sex or age. The prevalence of bothersome GERD symptoms was significantly higher in subjects with GERD than in those without GERD. CONCLUSION: Approximately 6.6% of Japanese have GERD and most persons with GERD described heartburn or acid regurgitation as bothersome.     

Definition for idiopathic gastric acid hypersecretion

Zollinger-Ellison syndrome and other gastric acid hypersecretory states in which a specific etiology is identified are defined as a basal acid output of greater than 15.0 meq/hr. To determine the level of basal acid output that defines idiopathic gastric hypersecretion, basal acid outputs were investigated in normal subjects and patients with duodenal ulcers, and functional and statistical definitions for idiopathic gastric acid hypersecretion were developed. Sixty-five normal subjects were evaluated to define idiopathic gastric acid hypersecretion on a statistical basis, and 22 patients with refractory duodenal ulcers were evaluated to define idiopathic gastric acid hypersecretion on a functional basis. Mean basal acid output for the 65 normal subjects was 3.0±2.7 meq/hr. Even though the mean basal acid output for the group of 28 normal male subjects was slightly higher than for the group of 37 normal female subjects, the groups were not significantly different. The 95% confidence interval around the mean basal acid output for all normal subjects was 2.4–3.7 meq/hr, with little difference between the male and female groups. The mean basal acid output plus two standard deviations and the mean basal acid output plus three standard deviations for the 65 normal subjects were 8.4 meq/hr and 11.1 meq/hr, respectively. Of 109 patients with active duodenal ulcers treated for eight weeks with standard doses of antisecretory medication, 22 showed no healing as documented by endoscopy. The mean basal acid output for these 22 patients with nonhealed duodenal ulcers was 18.7 meq/hr (range 10.1–49.1 meq/hr) while mean basal acid output for the 87 patients with healed duodenal ulcers was 7.5 meq/hr (range 0.0–27.9 meq/hr). The difference in mean basal acid output between these two groups was statistically different (P<0.001). All patients with refractory duodenal ulcers had basal acid outputs of greater than 10.0 meq/hr. Our results indicate that the definition for idiopathic gastric acid hypersecretion should be a basal acid output of greater than 10.0 meq/hr, since, based on refractory duodenal ulcer disease, the functional definition for idiopathic gastric acid hypersecretion is a basal acid output of greater than 10.0 meq/hr, which in our data also corresponds well to the statistically defined range of basal acid output in normal subjects.     

Prevalence of gastroesophageal reflux disease and gastroesophageal reflux disease symptoms in Japan

Background and Aim:  Epidemiological studies have shown that 10–48% of people in developed countries have gastroesophageal reflux disease (GERD) symptoms such as heartburn and acid regurgitation. The present study aimed to examine the prevalence of GERD symptoms and GERD in Japanese subjects.
Methods:  A cross-sectional study of Japanese subjects who visited a clinic for a routine health check up was carried out. Subjects were asked to fill out a self-report questionnaire. GERD was defined as the presence of heartburn and/or acid regurgitation at least twice per week.
Results:  Of the 6035 eligible subjects, 2662 (44.1%) reported having had heartburn and/or acid regurgitation during the past year: 124 (2.1%) daily, 275 (4.6%) twice per week, 773 (12.8%) twice per month and 1490 (24.7%) less than twice per month. Three hundred and ninety-nine (6.6%) subjects were diagnosed as having GERD and there was no relationship between the prevalence of GERD and either sex or age. The prevalence of bothersome GERD symptoms was significantly higher in subjects with GERD than in those without GERD.
Conclusion:  Approximately 6.6% of Japanese have GERD and most persons with GERD described heartburn or acid regurgitation as bothersome.     

慢性阻塞性肺病与胃食管反流病

目的：了解慢性阻塞性肺病(COPD)患者中胃食管反流病(GERD)的发生率及探讨GERD与COPD的关系。方法：从医院门诊收集89例COPD患者[第1秒用力呼气量(FEV_1)=1．37±0．53],同时选取88例非COPD患者为对照组,所有病例完成反流性疾病诊断问卷、慢性黏液高分泌症(CMH)问卷和肺功能检查。结果：COPD组中GERD发生率为18%,对照组为16%。气道阻塞严重(根据肺功能判断)的COPD患者没有更高的GERD发生率,各不同严重程度的COPD患者的GERD发生率分别为11%(轻度)、24%(中度)、11%(重度)和19%(极重度)。气促程度严重的COPD患者中GERD发生率较气促程度轻者升高(29%比15%,P=0．19)。有CMH的患者中27%表现GERD,而无CMH患者中仅8%表现GERD(P＜0．05)。结论：本研究发现COPD患者中GERD的发生率没有明显增高,但气促症状严重的患者表现较高的GERD发病率。CMH与GERD有显著的相关性,提示CMH的潜在作用及在治疗有CMH的COPD患者时需考虑GERD影响。     

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目的探讨非糜烂性胃食管反流病不同于反流性食管炎的发病机制。方法选择1996～2004年北京大学人民医院因反酸、胃灼热感等反流症状确诊为胃食管反流病患者57例,按照内镜下食管黏膜有无破损分为非糜烂性胃食管反流病组和反流性食管炎组,比较两组的一般情况、反流症状、是否合并H.pylori(Hp)感染,以及食管动力测定和食管胃24hpH监测结果。结果两组患者年龄、性别、烟酒嗜好等一般情况及合并Hp感染情况比较差异无显著性。非糜烂性胃食管反流病组不典型反流症状(胸骨后痛)的发生率明显高于反流性食管炎组。两组患者都存在病理性酸反流,但两组患者之间酸和(或)碱反流比较无差异。非糜烂性胃食管反流病患者的食管体部各段蠕动波峰值明显高于反流性食管炎患者。非糜烂性胃食管反流病患者卧位胃酸分泌高于反流性食管炎患者。结论非糜烂性胃食管反流病的不典型反流症状发生率更高。在两组发病机制异同上,反流的强弱并非主要因素,重要的是食管防御机制的差别。     

反流性疾病问卷表在军人胃食管反流病中的诊断价值

[目的]探讨反流性疾病问卷表(RDQ)在军人胃食管反流病(GERD)中的诊断价值。[方法]采用多阶段、分层、整群随机抽样的方法对驻闽某部军人进行反流性疾病问卷调查,记录被调查者过去4周内烧心、非心源性胸痛、反酸和反流4种症状出现的频率和程度积分,以RDQ评分≥12分作为GERD的诊断标准,计算军人中GERD的患病率,同时分析经电子胃镜检查证实为反流性食管炎(RE)患者的RDQ评分情况。[结果]研究得出军人GERD的患病率为6.77%,经胃镜检查420例中明确诊断为RE 60例(RE组)和内镜检查正常360例(非RE组)的RDQ评分差异有统计学意义(P0.01),说明评分与发生RE之间有较大关联。[结论]RDQ评分量表可以作为初步诊断军人GERD的一个良好的筛选试验。     

Temporal correlation between chronic cough and gastroesophageal reflux disease

Reflux disease (GERD) and chronic cough often coexist, but a temporal correlation using the symptom association probability has not been reported. Our aim was to determine if a temporal correlation exists between cough and GERD. Sixty-one patients with chronic cough had esophageal pH monitoring with sensors 5 and 20 cm above the LES. The symptom (SI) and symptom sensitivity (SSI) indices and the symptom association probability (SAP) were used to test cough–reflux association. Pathological reflux was defined as the percentage of time pH <4 exceeded 4.2%. A significant temporal association between cough and distal reflux was made in 35% of patients by SAP compared with only 14.8% by SI and SSI alone (P < 0.002). Patients with pathologic reflux had a greater likelihood of a temporal symptom correlation (57.1%) when not on acid-blocking medications. In conclusion, a temporal association between cough and distal reflux exists in one third of patients, especially those with pathological reflux. The SAP is a more sensitive measure of temporal association than SI or SSI.     

Multichannel intraluminal impedance and pH monitoring in gastroesophageal reflux disease

The role of acid is very well established in the pathogenesis of gastroesophageal reflux disease and acid suppression constitutes the main approach to its medical treatment. With the current frequent use of proton pump inhibitors, we are seeing increasing numbers of patients in whom symptoms persist despite pharmacological acid suppression. Reflux monitoring has been traditionally performed through esophageal pH measurement to detect acid reflux (i.e., drops in esophageal pH to below 4.0). Multichannel intraluminal impedance and pH measurement constitutes an important development in reflux monitoring because, in addition to detecting acid reflux, it enables measurement of nonacid reflux (i.e., with a pH > 4.0, also known as ‘weakly acidic’ for pH > 4 but < 7, or ‘weakly alkaline’ if pH > 7), which may be responsible for symptoms in some patients who are being treated with proton pump inhibitors. This review describes the approach to measuring nonacid reflux, the possible mechanisms responsible for symptoms due to this type of reflux, the clinical importance of this phenomenon and available treatment options; and the role of multichannel intraluminal impedance and pH monitoring in the evaluation of refractory gastroesophageal reflux disease.     

Prevalence and clinical picture of gastroesophageal prolapse in gastroesophageal reflux disease

The prevalence of gastroesophageal (GE) mucosal prolapse in patients with gastroesophageal reflux disease (GERD) was investigated as well as the clinical profile and treatment outcome of these patients. Of the patients who were referred to our service between 1980 and 2008, those patients who received a complete diagnostic work-up, and were successively treated and followed up at our center with interviews, radiology studies, endoscopy, and, when indicated, esophageal manometry and pH recording were selected. The prevalence of GE prolapse in GERD patients was 13.5% (70/516) (40 males and 30 females with a median age of 48, interquartile range 38-57). All patients had dysphagia and reflux symptoms, and 98% (69/70) had epigastric or retrosternal pain. Belching decreased the intensity or resolved the pain in 70% (49/70) of the cases, gross esophagitis was documented in 90% (63/70) of the cases, and hiatus hernias were observed in 62% (43/70) of the cases. GE prolapse in GERD patients was accompanied by more severe pain (P < 0.05) usually associated with belching, more severe esophagitis, and dysphagia (P < 0.05). A fundoplication was offered to 100% of the patients and was accepted by 56% (39/70) (median follow up 60 months, interquartile range 54-72), which included two Collis-Nissen techniques for true short esophagus. Patients who did not accept surgery were medically treated (median follow up 60 months, interquartile range 21-72). Persistent pain was reported in 98% (30/31) of medical cases, belching was reported in 45% (14/31), and GERD symptoms and esophagitis were reported in 81% (25/31). After surgery, pain was resolved in 98% (38/39) of the operative cases, and 79% (31/39) of them were free of GERD symptoms and esophagitis. GE prolapse has a relatively low prevalence in GERD patients. It is characterized by epigastric or retrosternal pain, and the need to belch to attenuate or resolve the pain. The pain is allegedly a result of the mechanical consequences of prolapse of the gastric mucosa into the esophagus.     

Pharmacologic management and treatment of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is one of the most common diagnoses in daily practice. Diagnosis can be made on symptom evaluation, on pH-monitoring or on endoscopic findings. In contrast to commonly held opinion there is no strong evidence that lifestyle factors are a dominant factor in the pathophysiology of GERD. The various agents currently used for treatment of GERD include mucoprotective substances, antacids, H(2)-blockers and proton pump inhibitors. This article gives an overview of the pharmacological management of GERD and focuses on the differential therapy of endoscopy-negative GERD, GERD with esophagitis and maintenance therapy.     

An early cancer of the gastric cardia arising from carditis after long-term gastroesophageal reflux disease in the absence of Helicobacter pylori infection

We describe an early gastric cardiac cancer in a patient who had suffered long-term gastroesophageal reflux disease (GERD) but showed no evidence of infection with Helicobacter pylori. Proximal gastrectomy and partial resection of the lower esophagus was performed. Histological examination revealed the lesion to be a gastric cardiac adenocarcinoma, which had partially invaded the submucosal layer. Intestinal metaplasia was also found in some areas. Inflammation, however, appeared to be limited to the gastric cardia. This cancer may have arisen via a sequence of carditis and cardiac intestinal metaplasia, due primarily to the GERD and not to H. pylori infection.