Study Of Pathogenic Factors, Pathogenesis, Diagnosis Of Primary Pathological Duodenogastric Reflux

Part One Relationship between primary pathological duodenogastric reflux and chronic inflammation of gastric mucosaObjective:To study the relationship among the gastric mucosal lesions caused by primary pathological DGR, Hp infection and the level of bile reflux assessed with 24-hour monitoring of bilirubin absorbance.Methods:1 Subjects:58 cases in primary pathological DGR group,30 males, 28 females,age from 18-year-old to 69-year-old.All cases were enrolled with established criteria.2 The level of the intragastric bile reflux in 24 hours was measured by Bilitec 2000 monitor . Time percentage of bilirubin absorbance≥0.25 was used as threshold to evaluate the severity of duodenogastric reflux. Endoscopy and gastric mucosa biopsies were performed in all cases for examination with rapid urease test, improved Giemsa staining and HE staining in order to diagnose Hp infection and define the lesions of gastric mucosa. The degree of chronic inflammation, activity, atrophy, intestinal metaplasia of gastric mucosa were observed according to the New Sydney system criteria. The lesions of gastric mucosa were classified into four degrees, which were normal, mild, moderate, and severe, scored as 0, 1, 2, 3. The total scores of gastric mucosal lesions degree were taken as New Sydney system pathological scores.Results:1 All cases were divided into two groups, Hp positive group(20 cases) and Hp negative group(38 cases) in primary pathological DGR group, based on the diagnosis of Hp infection. Based on the severity of bile reflux, all cases were divided into two groups, high reflux group(29 cases) and low reflux group(29 cases). Hp infection rate was 20.7%(6/29) in high reflux group and 48.3%(14/29) in low reflux group. Hp infection rate in high reflux group was significantly lower than that in low reflux group(P<0.05).2 The frequency of intestinal metaplasia of gastric antrum and anguli in high reflux group was significantly higher than that in low reflux group(P<0.05). The New Sydney system pathological scores of gastric antrum and anguli in Hp positive group were higher than that in Hp negative group(P<0.05),while the difference in pathological scores of gastric body between Hp positive group and Hp negative group showed no significance(P>0.05). The New Sydney system pathological scores of gastric antrum and anguli in high reflux group were higher than that in low reflux group(P<0.05), while the difference in pathological scores of gastric anguli and gastric body between high reflux group and low reflux group showed no significance(P>0.05).3 The time percentage of bilirubin absorbance≥0.25 in Hp positive group was significantly lower than that in Hp negative group(P<0.05), while the difference in short reflux frequency, long reflux frequency, longest reflux time,maximum,mean and median value of absorbance between Hp positive group and Hp negative group showed no significance(P>0.05).4 The time percentage of bilirubin absorbance≥0.25 was positively correlated with New Sydney system pathological scores of gastric antrum and gastric anguli in Hp positive group(r=0.567, P<0.05 and r=0.611, P<0.05), but was not correlated with that of gastric body(r=-0.419, P>0.05). The time percentage of bilirubin absorbance≥0.25 was positively correlated with New Sydney system pathological scores of gastric antrum and gastric anguli in Hp negative group(r=0.558, P<0.05 and r=0.406, P<0.05), but was not correlated with that of gastric body(r=0.313, P>0.05). The time percentage of bilirubin absorbance≥0.25 was not correlated with Dixon scores of gastric antrum, gastric anguli and gastric body in both Hp positive group and Hp negative group.Conclusion:1 Bile reflux is possibly the main cause to mucosal lesions of gastric antrum in primary pathological DGR and can attribute to intestinal metaplasia of gastric mucosa. Along with intensification of bile reflux, the mucosal lesions of gastric antrum aggravate.2 Bile reflux may inhibit Hp to locate in gastric antrum. Hp infection and bile reflux can contribute to mucosal lesions of gastric cooperatively.Part Two The investigation of relationship between electrogastrogram and gastric emptying in patients with primary pathological duodenogastric refluxObjective : To study the pathological factors by analyzing the relationship among the bile refiux degrees, electrogastrogram (EGG) rhythm changes and gastric emptying in primary pathological duodenogastric reflux (DGR) patients.Methods:1 Subjects:58 cases in primary pathological DGR group, the same as the fist part above. 21 healthy subjects were recruited as normal control, 13 males, 8 females, age from 19-year-old to 26-year-old. Two groups were enrolled with established criteria.2 58 cases of primary pathological DGR patients and 21 healthy persons (control group) were detected by EGG and gastric emptying test.Results:1 The patients of primary pathological DGR with fasting and postprandial frequency, the percentage of normal gastric slow wave, fasting / postprandial power ratio (PR) were lower than the control group (P <0.05). The patients of DGR with fasting and postprandial gastric percentage of bradygastria, tachygastria were higher than the control group (P <0.05).2 The fasting and postprandial dominant frequency, the percentage of normal gastric slow wave, fasting / postprandial power ratio (PR) in patients with high reflux were lower than that of the low reflux group (P <0.05). The percentage of bradygastria and tachygastria in high reflux group was higher than that of the low reflux group (P <0.05). 3 There was no significance of the fasting and postprandial gastric electrical parameters between Hp-positive and Hp-negative groups (P> 0.05).4 The gastric emptying in DGR group was lower than the control group. The gastric emptying delay in DGR group was increased than the control group significantly (P <0.05). The gastric emptying delay in high-reflux group and low group reflux was no difference (P> 0.05).Conclusion:1. There were abnormal gastric myoelectrical activity and gastric motility dysfunction in patients with primary pathological DGR, which may play an important role in pathological duodenogastric reflux.2. There was no correlation between with the fasting and postprandial gastric electrical parameters and Hp infection.Part Three Research on expression of Ghrelin in gastric mucosa of patients with primary pathological duodenogastric reflux Objective:To investigate the pathogenesis of gastric mucosa injury and the expression of Ghrelin in gastric mucosa in patients with primary pathological duodenogastric reflux (DGR).Methods:1 Subjects:The same as the second part above.2 Gastroscopy, histologic examination of gastric mucosal biopsy sample and 24-hour intragastric bilirubin monitoring with Bilitec 2000 were performed in 58 patients with primary pathological DGR. Immunohistochemical staining was used to detect the expression of Ghrelin in gastric mucosa epithelium cell. The patients were divided into the high reflux group (29 patients) and the low reflux group (29 patients) based on the severity of bile reflux.Results:1 The expression of Ghrelin in gastric mucosa epithelium cell in primary pathological DGR group was lower than that in control group (P<0.05). The difference of the expression of Ghrelin in gastric mucosa between high reflux group and low reflux group was significant (P<0.05). 2 The expression of Ghrelin in chronic superficial gastritis(CSG), chronic atrophy gastritis(CAG), intestinal metaplasia(IM) and dysplasia(DYS) was lower than that in the control subjects (P<0.05). The expression of Ghrelin in chronic atrophy gastritis was lower than that in chronic superficial gastritis and metaplasia (P<0.05).3 The expression of Ghrelin in gastric mucosa epithelium cell in Hp positive group was significantly lower than that in Hp negative group (P<0.05).Conclusion:1 Delayed gastric emptying may be attributive to the pathogenesis for primary pathological duodenogastric reflux. It may be related to the decreased Ghrelin expression in gastric mucosal tissue.2 Bile reflux contributes a lot to mucosal lesions in the whole stomach. Ghrelin had protective effect against gastric mucosal injuries.3 Hp infection may affect the expression of Ghrelin in gastric mucosal tissue.Part Four Investigation of cell proliferation and apoptosis of gastric mucosa in patients with primary pathological duodenogastric reflux Objective:To investigate the effects of cell proliferation and apoptosis on the development of gastric mucosal injury in patients with primary pathological duodenogastric reflux (DGR).Methods:1 Subjects:The same as the second part above.2 Gastroscopy, histologic examination of gastric mucosal biopsy sample and 24-hour intragastric bilirubin monitoring with Bilitec 2000 were performed in 58 patients with primary pathological DGR. Immunohistochemical staining was used to detect the expression of Ki-67 and Bcl-2. Cell apoptosis in gastric mucosa was determined by TUNEL technique. The patients were divided into the high reflux group (29 patients) and the low reflux group (29 patients) based on the severity of bile reflux.Results: 1 Proliferating index (PI) and apoptosis index (AI) in patients with primary pathological DGR were significantly higher than those in control group (P<0.05). The differences of PI and AI between high reflux group and low reflux group were significant (P<0.05).2 The PI and AI in normal gastric mucosa, chronic superficial gastritis, chronic atrophic gastritis and intestinal metaplasia were increased gradually. The difference between PI and AI showed significance in all groups (P<0.05) except the PI in chronic atrophic gastritis and intestinal metaplasia. PI and AI in chronic superficial gastritis, chronic atrophic gastritis and intestinal metaplasia were positively correlated. From chronic atrophic gastritis to intestinal metaplasia to gastric epithelial dysplasia, PI was still increased, but AI decreased in gastric epithelial dysplasia. AI and PI were negatively correlated (r=-0.72).3 The positive expression rates of Ki-67 in Dys were significant higher than other groups (P<0.05). The positive expression rates of Bcl-2 in Dys were significant higher than those groups (P<0.05).Conclusion:1 Disturbances in cell proliferation and apoptosis may be one of the major pathogenesis of gastric mucosa injury and cell canceration in patients with primary pathological DGR.2 The over-expression of Ki-67 and Bcl-2 in CAG, IM and Dys may play a key role in the development of gastric cancer.Part Five The study of porphobilin staining of gastric mucosa on diagnosis of primary pathological duodenogastric refluxObjective:To study the value of porphobilin staining of gastric mucosa on diagnosis of primary pathological duodenogastric reflux.Methods:1 Subjects:The same as the second part above.2 Endoscopy, histologic examination and 24-hour intragastric bilirubin monitoring with Bilitec 2000 were performed in 58 patients with primary pathological duodenogastric reflux. And porphobilin staining of gastric mucosa was measured by quantitative diagnosis.Results:1 The deposition of porphobilin in mucosa of gastric antrum, gastric anguli and gastric body in primary pathological DGR group were significantly severer than that in normal group(P<0.05). The deposition of porphobilin in mucosa of gastric antrum and gastric anguli were significantly severer than that of gastric body in primary pathological DGR group(P<0.05). The deposition of porphobilin in mucosa of gastric antrum, gastric anguli and gastric body in high reflux group were significantly severer than that in low reflux group (P<0.05). The deposition of porphobilin in mucosa of gastric antrum and gastric anguli were significantly severer than that of gastric body in the two groups (P<0.05).2 The deposition of porphobilin in mucosa of gastric antrum and gastric anguli were positively correlated with New Sydney system pathological scores of gastric antrum and gastric anguli in primary pathological DGR group(r=0.59, P<0.05 and r=0.73, P<0.05). The deposition of porphobilin in mucosa of gastric body was not correlated with New Sydney system pathological scores of gastric body in primary pathological DGR group (r=-0.33, P>0.05).Conclusion:Porphobilin staining of mucosa in gastric antrum is of good correlation with severity of bile reflux and gastric mucosal lesion. It may be an important evidence for diagnosis of primary pathological DGR.