邹议消化内科门诊胃食管反流病的临床分析

目的:针对于消化内科门诊中胃食反流的临床病例进行研究分析。方法:选取我院2015~2016年间门诊病例中胃食反流患者中的70例作为研究对象,按照随机分配,分为对照组和研究组,每组各35例患者,对照组采用雷尼替丁进行治疗,研究组采用奥美拉唑进行治疗^([1]),并对两组患者治疗后的效果进行分析。结果:两组患者治疗后出现了明显差异,在总有效率方面研究组患者99.9%明显高于对照组总有效率94.1%,P<0.05具有统计学意义。结论:胃食反流患者给予奥美拉唑治疗效果要比雷尼替丁效果优,不仅改善了患者临床中的症状,提高治愈率,并且对患者的心理压力以及经济负担都有所减轻,值得在临床中应用推广。

Multicenter Clinical Randomized Controlled Trial and Network Pharmacology Analysis of Zhenzhu Qingyuan Granules for the Treatment of Gastroesophageal Reflux Disease

Objective To evaluate the clinical efficacy and safety of Zhenzhu Qingyuan Granules through a clinical randomized controlled trial and to analyze the potential action targets and pathways of this formula using network pharmacology.Methods Patients with gastroesophageal reflux disease(GERD)of liver–stomach stagnant heat pattern who met the inclusion and exclusion criteria were randomly divided into the control group and the observation group.The control group received oral rabeprazole,whereas the observation group were given Zhenzhu Qingyuan Granules in addition to the rabeprazole.The treatment duration was 8 weeks.Clinical efficacy was observed in both groups after 8 weeks.Network pharmacology was used to analyze the action targets of ZhenzhuQingyuanGranules and the genes related to GERD,and core targets were inferred.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to explore the potential mechanisms of this formula.Results The clinical research results showed that the total effective rate in the treatment group was 92.68%,compared with 70.00%in the control group,with a statistically significant difference(p<0.05).After treatment,both Chinese medicine syndrome score and endoscopic score improved in both groups compared with before treatment(p<0.05),and the treatment group showed greater improvement than the control group(p<0.05).Network pharmacology identified effective components of Zhenzhu Qingyuan Granules for treating GERD,including quercetin,luteolin,andβ-sitosterol,with potential action targets such as tumor protein 53(TP53),protein kinase B(AKT1),and tumor necrosis factor.Conclusion Zhenzhu Qingyuan Granules can significantly improve clinical symptoms in patients with GERD of liver–stomach stagnated heat pattern,enhance clinical efficacy,and have high safety.This formula may exert therapeutic effects through multiple targets and pathways.

Risk factors for gastroesophageal reflux disease,reflux esophagitis and non-erosive reflux disease among Chinese patients undergoing upper gastrointestinal endoscopic examination

AIM: To analyze the spectrum and risk factors of gastroesophageal reflux disease (GERD) based on presenting symptoms and endoscopic f indings. METHODS: A cross-sectional survey in a cluster random sample was conducted from November 2004 to June 2005 using a validated Chinese version Reflux Disease Questionnaire (RDQ) and other items recording the demographic characteristics and potential risk factors for GERD. Subjects were def ined as having GERD symptoms according to the RDQ score (> 12). All subjects were endoscopied and the def inition and severity of erosive esophagitis were evaluated by Los Angeles classif ication. The statistical analysis was performed with SPSS13.0 programs. RESULTS: Of 2231 recruited participants, 701 (31.40%) patients were diagnosed as having GERD while 464 (20.80%) patients had objective findings of reflux esophagitis (RE). Of those 464 patients, only 291 (13.00%) were reported as subjects with GERD symptoms. A total of 528 (23.70%) patients were found to have GERD symptoms, including 19.50% patients with grade A or B reflux esophagitis, 0.90% with grade C and 0.40% with grade D. On multivariate analysis, old age, male, moderate working burden, divorced/widowed and strong tea drinking remained as signif icant independent risk factors for erosive esophagitis. Meanwhile, routine usage of greasy food and constipation were considered as significant independent risk factors for non-erosive reflux disease (NERD). CONCLUSION: GERD is one of the common GI diseaseswith a high occurrence rate in China and its main associated factors include sex, anthropometrical variables and sociopsychological characteristics.

Body weight, lifestyle, dietary habits and gastroesophageal reflux disease

While lifestyle modifications are currently used as firstline treatment for subjects with gastroesophageal reflux disease (GERD), the pathogenetic role of lifestyle factors and consequently, the efficacy of lifestyle measures is controversial. Our aim was to systematically review the pathogenetic link between overweight/ obesity, dietary habits, physical activity and GERD, and the beneficial effect of specific recommended changes, by means of the available literature from the 1999 to the present. Obesity, in particular, abdominal obesity, plays a key role in determining GERD symptoms and complications through mechanical and metabolic effects. Controlled weight loss (by diet or surgery) is effective in improving GERD symptoms. No definitive data exist regarding the role of diet and, in particular, of specific foods or drinks, in influencing GERD clinical manifestations. Moderate physical activity seems to be beneficial for GERD, while vigorous activity may be dangerous in predisposed individuals. In conclusion, being obese/overweight and GERD-specific symptoms and endoscopic features are related, and weight loss significantly improves GERD clinical-endoscopic manifestations. The role of dietary behavior, mainly in terms of specific dietary components, remains controversial. Mild routine physical activity in association with diet modifications, i.e. a diet rich in fiber and low in fat, is advisable in preventing reflux symptoms.

Prevalence of linked angina and gastroesophageal reflux disease in general practice

AIM： To evaluate the association between gastroesophageal reflux diseases （GERD） and coronary heart diseases. METHODS： One thousand nine hundred and seventy consecutive patients who attended our hospital were enrolled. All of the patients who first attend our hospital were asked to respond to the F-scale questionnaire regardless of their chief complaints. All patients had a careful history taken, and resting echocardiography （ECG） was performed by physicians if the diagnostic necessity arose. Patients with ECG signs of coronary artery ischemia were defined as ST- segment depression based on the Minnesota code. RESULTS： Among 712 patients （36%） with GERD, ECG was performed in 171 （24%）, and ischemic changes were detected in eight （5%）. Four （50%） of these patients with abnormal findings upon ECG had no chest symptoms such as chest pain, chest oppression, or palpitations. These patients （0.6%; 4/712） were thought to have non-GERD heartburn, which may be related to ischemic heart disease. Of 281 patients who underwent ECG and did not have GERD symptoms, 20 （7%） had abnormal findings upon ECG. In patients with GERD symptoms and ECG signs of coronary artery ischemia, the prevalence of linked angina was considered to be 0.4% （8/1970 patients）.CONCLUSION： The present study suggested that ischemic heart disease might be found although a patient was referred to the hospital with a complaint of GERD symptoms. Physicians have to be concerned about missing clinically important coronary artery disease while evaluating patients for GERD symptoms.

Is obesity associated with gastropharyngeal reflux disease?

AIM: To examine the association between obesity and gastropharyngeal reflux disease (GPRD) as well as gastroesophageal reflux disease (GERD) METHODS: We conducted a cross-sectional study of consecutive patients undergoing ambulatory 24-h dual-probe pH monitoring from July 2003 to December 2006. The association between body mass index (BMI) and parameters about gastroesophageal or gastropharyngeal reflux was examined in univariate and multivariate analyses.RESULTS: A total of 769 patients (307 men and 462 women; mean age 50.7 years) were finally enrolled. Most variables showing gastroesophageal reflux was higher in the obese patients than the patients with normal BMI. There was no difference in all the variables showing gastropharyngeal reflux according to the BMI. After adjustment for age, sex, alcohol intake and smoking, obese patients demonstrated an about 2-fold increase in risk of GERD compared with patients with normal BMI (OR, 1.9; 95 CI, 1.3-2.9), but overweight patients did not demonstrate increased risk of GERD (OR, 1.2; 95 CI, 0.8-1.7). Both obese patients and overweight patients did not demonstrated increased risk of GPRD compared with patients with normal BMI (OR, 1.1; 95 CI, 0.8-1.7; and OR, 0.9; 95 CI, 0.6-1.3, respectively).CONCLUSION: Obesity is not associated with GPRD reflux while it is associated with GERD.

Neuro-regulation of lower esophageal sphincter function as treatment for gastroesophageal reflux disease

The junction between the esophagus and the stomach is a specialized region, composed of lower esophageal sphincter (LES) and its adjacent anatomical structures, the gastric sling and crural diaphragm. Together these structures work in a coordinated manner to allow ingested food into the stomach while preventing reflux of gastric contents across the esophago-gastric junction (EGJ) into the esophagus. The same zone also permits retrograde passage of air and gastric contents into esophagus during belching and vomiting. The precise coordination required to execute such a complicated task is achieved by a finely-regulated high-pressure zone. This zone keeps the junction between esophagus and stomach continuously closed, but is still able to relax briefly via input from inhibitory neurons that are responsible for its innervation. Alterations of the structure and function of the EGJ and the LES may predispose to gastroesophageal reflux disease (GERD).

Laryngopharyngeal reflux in patients with reflux esophagitis

AIM: To assess the prevalence of laryngopharyngeal reflux (LPR) in patients with reflux esophagitis and dis-close factors contributing to the development of LPR. METHODS: A total of 167 patients who proved to have reflux esophagitis by endoscopy were enrolled. They received laryngoscopy to grade the reflux find-ings for the diagnosis of LPR. We used validated ques-tionnaires to identify the presence of laryngopharyn-geal symptoms, and stringent criteria of inclusion to increase the specificity of laryngoscopic findings. The data of patients were analyzed statistically to find out factors related to LPR. RESULTS: The prevalence rate of LPR in studied sub-jects with reflux esophagitis was 23.9%. Age, hoarse- ness and hiatus hernia were factors significantly as-sociated with LPR. In 23 patients with a hiatus hernia, the group with LPR was found to have a lower trend of esophagitis grading. CONCLUSION: Laryngopharyngeal reflux is present in patients with reflux esophagitis, and three predicting factors were identified. However, the development of LPR might be different from that of reflux esophagi-tis. The importance of hiatus hernia deserves further study.

Controversies in the treatment of gastroesophageal reflux and achalasia

The immense success of laparoscopic surgery as an effective treatment of gastroesophageal reflux disease （GERD） and achalasia has established minimal invasive surgery as the gold standard for these two conditions with lower morbidity and mortality, shorter hospital stay, faster convalescence, and less postoperative pain. One controversy in the treatment of GERD evolves around laparoscopic antireflux surgery （LAP, S） as the preferred treatmerit for Barrett＇s esophagus and the procedure＇s potential to reduce the risk of adenocarcinoma of the esophagus. GERD has also been associated with respiratory symptoms, asthma and laryngeal injury, and a second controversy prompts discussions about whether total or partial fundoplication is the more appropriate treatment for GERD. A new and promising alternative in the treatment of GERD is endoluminal therapy. Three types of this new treatment option will be discussed： radiofrequency energy delivered to the lower esophageal sphincter, the creation of a mechanical barrier at the gastroesophageal junction, and the direct endoscopic tightening of the lower esophageal sphincter. Laparoscopic surgery is discussed not only as a very effective treatment for GERD but also as permanent cure for achalasia. This review analyzes the three most important treatment options for achalasia： medications, pneumatic dilatation, and surgical therapy. Medications as the only true non-invasive option in the treatment of achalasia are not as effective as LAPS because of their short half-life and variable absorption due to the poor esophageal emptying. The second treatment option, pneumatic dilatation, involves the stretching of the lower esophagus and is still considered the most effective nonsurgical treatment for achalasia. Finally, surgical therapy for achalasia and the two major controversies concerning this laparoscopic treatment are discussed. The first involves the extent to which the myotomy is extended onto the stomach, and the second concerns the necessity and type of antireflux procedure to prevent GERD after myotomy. LAPS and laparoscopic Heller myotomy are the agreed upon as the gold standards for surgical treatment of GERD and achalasia, respectively. In the hands of an experienced laparoscopic surgeon both are safe and effective treatments for patients with excellent subjective and objective long-term results with at least 90% patient satisfaction.

Ten mg dexrabeprazole daily is as effective as 20 mg dexrabeprazole daily

Ten mg dexrabeprazole daily has been shown to be more effective than 20 mg rabeprazole daily against gastroesophageal reflux disease (GERD). This report shows that the efficacy of 10 mg dexrabeprazole daily is equivalent to that of 20 mg dexrabeprazole daily against GERD. This implies that a dose of 10 mg dexra- beprazole is sufficient to block the maximum amount of proton pumps without any need to double the dose as suggested with rabeprazole.

Synchronous electrogastrographic and manometric study of the stomach as an esophageal substitute

AIM: To investigate the electric and contractile mechanisms involved in the deranged function of the transposed stomach in relation to the course of the symptoms and the changes in contractile and electrical parameters over time.METHODS: Twenty-one patients after subtotal esophagectomy and 18 healthy volunteers were studied.Complaints were compiled by using a questionnaire, and a symptom score was formed. Synchronous electrogastrography and gastric manometry were performed in the fasting state and postprandially.RESULTS: Eight of the operated patients were symptomfree and 13 had symptoms. The durations of the postoperative periods for the symptomatic (9.1±6.5 mo)and the asymptomatic (28.3±8.8 mo) patients were significantly different. The symptom score correlated negatively with the time that had elapsed since the operation. The percentages of the dominant frequency in the normogastric, bradygastric and tachygastric ranges differed significantly between the controls and the patients.A significant difference was detected between the power ratio of the controls and that of the patients. The occurrence of tachygastria in the symptomatic and the symptom-free patients correlated negatively both with the time that had elapsed and with the symptom score. There was a significant increase in motility index after feeding in the controls, but not in the patients. The contractile activity of the stomach increased both in the controls and in the symptom-free patients. In contrast, in the group of symptomatic patients, the contractile activity decreased postprandially as compared with the fasting state.CONCLUSION: The patients' post-operative complaints and symptoms change during the post-operative period and correlate with the parameters of the myoelectric and contractile activities of the stomach. Tachygastria seems to be the major pathogenetic factor involved in the contractile dysfunction.

Prevalence of gastroesophageal reflux symptoms in a large unselected general population in Japan

AIM:To examine the prevalence of gastroesophageal reflux disease (GERD) symptoms in a large unselected general population in Japan. METHODS: In Japan, mature adults are offered regular check-ups for the prevention of gastric cancer. A notice was sent by mail to all inhabitants aged > 40 years. A total of 160 983 Japanese (60 774 male, 100 209 female; mean age 61.9 years) who underwent a stomach check up were enrolled in this study. In addition, from these 160 983 subjects, we randomly selected a total of 82 894 (34 275 male, 48 619 female; mean age 62.4 years) to evaluate the prevalence of abdominal pain. The respective subjects were prospectively asked to complete questionnaires concerning the symptoms of heartburn, dysphagia, and abdominal pain for a 1 mo period. RESULTS: The respective prevalences of the symptoms in males and females were: heartburn, 15.8% vs 20.7%; dysphagia, 5.4% vs 7.8%; and abdominal pain, 6.6% vs 9.6%. Among these symptoms, heartburn was significantly high compared with the other symptoms, and the prevalence of heartburn was significantly more frequent in females than in males in the 60-89-year agegroup. Dysphagia was also significantly more frequent in female patients. CONCLUSION: The prevalence of typical GERD symptoms (heartburn) was high, at about 20% of the Japan population, and the frequency was especially high in females in the 60-89 year age group.

Heterogeneity of endoscopy negative heartburn:Epidemiology and natural history

It has now become clear that only about 40% or less of patients with heartburn and/or regurgitation have esophagitis, and that the majority of them lack visible distal esophageal mucosa breaks. These subjects are referred to as non-erosive gastroesophageal reflux disease (NERD) patients. It has been estimated that in the Western world at least one tenth of the general population has at least weekly heartburn. This proportion seems to be lower in Asia, while prevalence is rapidly increasing. Although it would be extremely useful to have prospective information regarding the fate of such patients, the natural history of NERD is largely unknown, and very few studies in the literature have addressed this issue. These studies are for the greater part old, not well conducted, and suffer from methodological drawbacks including ill-defined entry criteria. However, a review of these studies indicates that a consistent minority of NERD patients may develop erosive disease at an approximate rate of about 10% per year.

Metabolic changes in the lower esophageal sphincter influencing the result of anti-reflux surgical interventions in chronic gastroesophageal reflux disease

AIM: With the availability of a minimally invasive approach, anti-reflux surgery has recently experienced a renaissance as a cost-effective alternative to life-long medical treatment in patients with gastroesophageal reflux disease (GERD). We are not aware of the fact whether reflux episodes causing complaints for a long time i.e., at least for one year are associated with metabolic changes in the lower esophageal sphincter, and if so, whether these may influence functional results achieved after anti-reflux surgery. METHODS: Between 1 January 2001 and 31 December 2002 we performed anti-reflux surgery on 79 patients. Muscle samples were taken from the lower esophageal sphincter (LES) in 33 patients during anti-reflux surgery. Inclusion criteria were: LES resting pressure below 10 mmHg and a marked, pH proven acid exposure to the esophagus of at least one year's duration, causing subjective complaints and requiring continuous proton pump inhibitor treatment. Control samples were obtained from muscle tissue in the gastroesophageal junction that had been removed from 17 patients undergoing gastric or esophageal resection. Metabolic and lysosomal enzyme activities and special protein concentrations 16 parameters in total were evaluated in tissue taken from control specimens and tissue taken from patients with GERD. The biochemical parameters of these intra-operative biopsies were used to correlate the results of anti-reflux operations (Visick Ⅰ and Ⅱ-Ⅲ). RESULTS: In the reflux-type muscle, we found a significant increase of the energy-enzyme activities e.g., creatine kinase, lactate dehydrogenase, β-hydroxybutyrate dehydrogenase, and aspartate aminotransaminase-. The concentration of the structural protein S-100 and the myofibrillar protein troponin Ⅰ were also significantly increased. Among lysosomal enzymes, we found that the activities of cathepsin B, tripeptidyl-peptidase Ⅰ, dipeptidyl-peptidase Ⅱ, β-hexosaminidase B, β-mannosidase and β-galactosidase were significantly decreased as compared to the control LES muscles. By analyzing the activity values of the 9 patients in Visick groups Ⅱ and Ⅲ at two months post-surgery, we found a significant increase in the activity of the so-called energy-enzyme values and in the concentration of structural and myofibrillar proteins as compared to the rest of the reflux patients. CONCLUSION: Our results call attention to the metabolic changes that occurred in the LES muscles of reflux patients. The developing hypertrophy-like changes of LES muscles may be a reason for complaints after anti-reflux surgery, which consisted mainly of reports of persisting dysphagia.

Esophageal cell proliferation in gastroesophageal reflux disease: Clinical-morphological data before and after pantoprazole

AIM: To evaluate esophageal mucosal defense mechanisms at an epithelial level to establish if pantoprazole treatment can induce ultrastructural healing and improvement in the proliferation activity of the esophageal epithelium in gastroesophageal reflux disease (GERD). METHODS: This was a single-blinded study for pHmonitoring, and histological, ultrastructural and MIB1 immunostaining evaluation. Fifty eight patients with GERD were enrolled and underwent 24 h pH-monitoring and endoscopy. Patients were treated for 12 and 24 mo with pantoprazole. Esophageal specimens were taken for histological and ultrastructural evaluation, before and after the treatment. RESULTS: With transmission electron microscopy, all patients with GERD showed ultrastructural signs of damage with dilation of intercellular spaces (DIS). After 3 mo of therapy the mean DIS values showed asignificant reduction and the mean MIB1-LI values of GERD showed an increase in cell proliferation. A further 3 mo of therapy significantly increased cell proliferation only in the erosive esophagitis (ERD) group. CONCLUSION: Three months of pantoprazole therapy induced ultrastructural healing of mucosal damage in 89% and 93% of ERD and non-erosion patients, respectively. Moreover, long-term pantoprazole treatment may be helpful in increasing the capability for esophageal cell proliferation in GERD, particularly in ERD patients.

Is ineffective esophageal motility associated with gastropharyngeal reflux disease?

AIM： TO evaluate the association between IEM and gastropharyngeal reflux disease （GPRD） in patients who underwent ambulatory 24-h dual-probe pH monitoring for the evaluation of supraesophageal symptoms. METHODS： A total of 632 patients who underwent endoscopy, esophageal manometry and ambulatory 24-h dual-pH monitoring due to supraesophageal symptoms （e.g. globus, hoarseness, or cough） were enrolled. Of them, we selected the patients who had normal esophageal motility and IEM. The endoscopy and ambulatory pH monitoring findings were compared between the two groups. RESULTS;： A total of 264 patients with normal esophageal motility and 195 patients with the diagnosis of IEM were included in this study. There was no difference in the frequency of reflux esophagitis and hiatal hernia between the two groups. All the variables showing gastroesophageal reflux and gastropharyngeal reflux were not different between the two groups. The frequency of GERD and GPRD, as defined by ambulatory pH monitoring, was not different between the two groups. CONCLUSION： There was no association between IEM and GPRD as well as between IEM and GERD. IEM alone cannot be considered as a definitive marker for reflux disease.

Eosinophilic esophagitis

Eosinophilic esophagitis is increasingly recognized in adults. The diagnosis is based on the presence of both typical symptoms and pathologic findings on esophageal biopsy. Patients usually present with dysphagia, food impaction and/or reflux-like symptoms, and biopsy of the esophagus shows more than 15 eosinophils per high-power fi eld. In addition, it is essential to exclude the presence of known causes of tissue eosinophilia such as gastroesophageal reflux disease, infections, malignancy, collagen vascular diseases, hypersensitivity, and inflammatory bowel disease. There are no standardized protocols for the therapy of eosinophilic esophagitis. A variety of therapeutic approaches including acid suppression, dietary modifications, topical corticosteroids and endoscopic dilation can be used alone or in combination.

Esophageal epithelial surface in patients with gastroesophageal reflux disease:An electron microscopic study

A/M： To investigate the intercellular spaces between the most superficially located esophageal epithelial cells in patients with gastroesophageal reflux disease （GERD）. METHODS： Eighteen patients with erosive esophagitis, 10 patients with non-erosive reflux disease （NERD）, and 18 normal asymptomatic volunteers were enrolled. Biopsy specimens were obtained from the lower esophageal mucosa without ulcer or erosion. Scanning electron microscopy was employed to investigate the tightness of the superficial cellular attachment. RESULTS： The intercellular space between the most superficially located epithelial cells in patients with erosive esophagitis or NERD was not different from that in asymptomatic healthy individuals. CONCLUSION： Widened luminal intercellular spaces of esophageal superficial epithelium are not responsible for the induction of reflux symptoms in patients with GERD.

Is there a changing trend in surgical management of gastroesophageal reflux disease in children?

Gastroesophageal reflux disease (GORD) is a pathological process in infants manifesting as poor weight gain, signs of esophagitis, persistent respiratory symptoms and changes in neurobehaviour. It is currently estimated that approximately one in every 350 children will experience severe symptomatic gastroesophageal reflux necessitating surgical treatment. Surgery for GORD is currently one of the common major operations performed in infants and children. Most of the studies found favour laparoscopic approach which has surpassed open antireflux surgery as the gold standard of surgical management for GORD.However, it must be interpreted with caution due to the limitation of the studies, especially the small number of subject included in these studies. This review reports the changing trends in the surgical treatment of GORD inchildren.

Outcome of nonerosive gastro-esophageal reflux disease patients with pathological acid exposure

AIM： To assess the management and outcome of nonerosive gastro-esophageal reflux disease （NERD） patients who were identified retrospectively, after a 5-year follow-up. METHODS： We included patients with gastro-esophageal reflux disease （GERD） symptoms who had a negative endoscopy result and pathological 24-h esophageal pH-monitoring while off therapy. We interviewed them after an average period of 5 years （range 3.5-7 years） by means of a structured questionnaire to assess presence of GERD symptoms, related therapy, updated endoscopic data and other features. We assessed predictors of esophagitis development by means of univariate and multivariate statistical analysis. RESULTS： 260 patients （137 women） were included. Predominant GERD symptoms were heartburn and regurgitation in 103/260 （40%）. 70% received a maintenance treatment, which was proton pump inhibitor （PPI） in 55% of cases. An average number of 1.5 symptomatic relapses per patient/year of follow-up were observed. A progression to erosive gastro-esophageal reflux disease （ERD） was found in 58/193 （30.0%） of patients undergoing repeat endoscopy; 72% of these were Los Angeles grade A-B. CONCLUSION： This study to ERD occurs in about 5% shows that progression of NERD cases per year, despite therapy. Only two factors consistently and independently influence progression： smoking and absence of PPI therapy.