Relation of gallbladder function and Helicobacter pylori infection to gastric mucosa inflammation in patients with symptomatic cholecystolithiasis

BACKGROUND: Inflammatory alterations of the gastric mucosa are commonly caused by Helicobacter pylori (Hp) infection in patients with symptomatic gallstone disease. However, the additional pathogenetic role of an impaired gallbladder function leading to an increased alkaline duodenogastric reflux is controversially discussed. AIM: To investigate the relation of gallbladder function and Hp infection to gastric mucosa inflammation in patients with symptomatic gallstones prior to cholecystectomy. PATIENTS: Seventy-three patients with symptomatic gallstones were studied by endoscopy and Hp testing. Methods: Gastritis classification was performed according to the updated Sydney System and gallbladder function was determined by total lipid concentration of gallbladder bile collected during mainly laparoscopic cholecystectomy. RESULTS: Fifteen patients revealed no, 39 patients mild, and 19 moderate to marked gastritis. No significant differences for bile salts, phospholipids, cholesterol, or total lipids in gallbladder bile were found between these three groups of patients. However, while only 1 out of 54 (<2%) patients with mild or no gastritis was found histologically positive for Hp, this infection could be detected in 14 (74%) out of 19 patients with moderate to marked gastritis. CONCLUSION: Moderate to marked gastric mucosa inflammation in gallstone patients is mainly caused by Hp infection, whereas gallbladder function is not related to the degree of gastritis. Thus, an increased alkaline duodenogastric reflux in gallstone patients seems to be of limited pathophysiological relevance.     

Clinical research on the relation of chronic gastritis and intragastric bile acids

Intragastric bile acids on fasting for 1 hour have been determined by radioimmunoassay and thin-layer chromatographic scanning in 102 cases of chronic gastritis. The results showed that all of intragastric conjunction bile acids were higher in chronic atrophic gastritis group than those in chronic superficial gastritis group. Both of their intragastric bile acids and nitrite levels increased significantly in patients whose gastric mucosa appeared acute inflammation, glandular atrophy and moderate or severe intestinal metaplasia. These findings suggest that bile acids may be implicated in premalignant histological changes of gastric mucosa such as chronic atrophic gastritis. Determining intragastric bile acids will reflect the degree and injurious effect of duodenogastric reflux.     

以胃黏膜胆汁酸浓度评估胆汁反流对胃黏膜组织的作用

背景:胃黏膜胆汁酸水平可直接反映胃黏膜细胞胆汁酸暴露的程度,并体现胆汁酸对胃黏膜的损伤程度。目的:探讨以胃黏膜组织胆汁酸浓度评估胆汁反流对胃黏膜病理改变的影响。方法:选取经内镜检查和黏膜胆汁酸浓度确诊的40例胆汁反流性胃炎患者和20例无胆汁反流性胃炎患者,评估幽门螺杆菌(H.pylori)检出率,行组织病理学评分,并分析胃黏膜胆汁酸浓度与组织病理学评分的相关性。结果:与无胆汁反流性胃炎患者相比,胆汁反流性胃炎患者H.pylori检出率无明显差异;胃窦、胃体黏膜组织胆汁酸含量显著升高(P0.05);胃窦黏膜慢性炎症和肠化生评分显著升高(P0.05),胃体黏膜慢性炎症、炎症活动性、萎缩和肠化生评分均显著升高(P0.05)。胆汁反流性胃炎患者胃窦、胃体组织病理学改变均与胆汁酸浓度相关(P0.05)。结论:以胃黏膜胆汁酸浓度评估的胆汁反流与胃黏膜病理损伤严重程度呈正相关。与无胆汁反流性胃炎相比,胃内胆汁反流主要加重胃体部组织病理学损伤。     

Relationship between gastrin cell number, serum, antral mucosa and luminal gastrin concentration and gastric acidity in antral atrophic gastritis.

The aim of our study was to investigate the relationship between gastrin producing cell density with antral mucosa, luminal and serum gastrin concentration in antral atrophic gastritis. Our study group consisted of 17 patients: six with mild atrophic gastritis, seven with moderate atrophic gastritis and four with severe atrophic gastritis. None of the patients had type-A atrophic gastritis but the body mucosa was affected by superficial gastritis at various extent in some. A group of 15 healthy subjects served as control. All subjects underwent gastroscopic examination with multiple bioptic sampling. Radioimmunoassay was used for gastrin determination and photomicroscopy for gastrin producing cell density assessment. Electron microscopy was used to assess the gastrin producing granule density index. Patients with moderate and severe atrophic gastritis showed a lower gastric acidity and acid output as compared to control. Serum gastrin did not show significant differences among the groups. In moderate and severe atrophic gastritis, gastrin producing cell granule density index, gastrin producing cell density and antral mucosa gastrin concentration were significantly lower when compared with control and decreased with advancing of the severity of atrophic gastritis. In atrophic gastritis, however, the latter two measurements were not correlated. In moderate and severe atrophic gastritis luminal gastrin concentration significantly increased, compared with control, after the severity of atrophic gastritis. Gastrin producing cell granule density index and luminal gastrin concentration showed a significant correlation with gastric pH. These data suggest that in antral atrophic gastritis with reduced gastric acidity, the decrement of gastrin producing cells is followed by gastrin producing cell hyperfunction with increased luminal release of gastrin.     

抗胆汁反流治疗对胃内幽门螺杆菌感染的影响

体外研究发现胆汁可抑制幽门螺杆菌（H.pylori)的生长，但人体内胆汁反流对H.pylori的作用尚不清楚。目的：探讨抗胆汁反流治疗对胃内H.pylori感染的影响。方法：50例经胃镜检查确诊有胆汁反流的慢性胃炎患者纳入本研究。取胃窦黏膜活检标本行组织病理学检查和快速尿素酶试验（RUT），用改良Giemsa染色、RUT或血清H.pylori-IgG检测H.pylori感染情况。患者接受铝碳酸镁治疗（1000mg.tid,4周），治疗结束后复查胃镜和H.pylori感染情况。结果：治疗前患者的H.pylori感染率为66．0％，H.pylori感染者在I、Ⅱ、Ⅲ级胆汁反流性胃炎中的分布无显著差异。治疗后共有48例患者接受胃镜复查，结果显示胃内胆汗反流程度较治疗前明显减轻，H.pylori感染率为64．6％，与治疗前相比无显著差异。合并H.pylori感染者的胃黏膜炎症细胞浸润较非H.pylori感染者为重，且肠化发生率（39．4％）与非H.pylori感染者（11．8％）相比有显著差异（P＜0．05）。结论：合并H.pylori感染胆汁反流患者的胃炎和肠化均较单纯胆汁反流者为重。抗胆汁反流治疗可有效缓解胆汁反流性胃炎，但未能改善胃黏膜的H.pylori感染情况。     

原发性病理性十二指肠胃反流致病的因素分析

目的 探讨原发性病理性十二指肠胃反流(DGR)胃黏膜病变、幽门螺杆菌(Hp)感染、胆汁反流之间的关系.方法 应用便携式胆汁监测仪监测86例原发性病理性DGR患者胃内24 h胆汁反流情况;另取胃黏膜组织活检,分别行快速尿素酶试验、改良Giemsa染色和HE染色,判断有无Hp感染,并观察胃黏膜慢性炎症、活动性、萎缩、肠化等组织学特征.结果 ①将患者根据有无Hp感染分为Hp阳性组和Hp阴性组,Hp阳性组胃窦部黏膜病理积分、胆红素吸收值≥0.25的时间百分比均显著低于Hp阴性组(P均＜0.05);两组胆红素吸收值≥0.25的时间百分比和胃窦、胃角部黏膜病理积分均呈显著正相关(P均＜0.05).②将患者根据胆汁反流程度分为高反流组和低反流组,高反流组Hp阳性率显著低于低反流组(P＜0.05),胃窦和胃角部黏膜肠上皮化生的检出率、胃窦部黏膜病理积分均显著高于低反流组(P均＜0.05).结论 原发性病理性DGR导致胃窦黏膜损伤的主要因素可能为胆汁反流,随胆汁反流程度加重,胃窦黏膜损伤程度加重;胆汁反流可能抑制Hp在胃窦部定植,Hp感染可能与胆汁反流协同作用导致胃体部黏膜损伤.     

A prospective study on duodenogastric reflux and on histological changes in gastric mucosa after cholecystectomy.

The authors carried out a prospective study to evaluate variations with time in postcholecystectomy duodenogastric reflux (expressed as "fasting bile reflux" in mumol/h) and in gastric mucosal damage. Ten patients underwent (before cholecystectomy, 6 months after surgery and after a median period of 4 years from surgery) a gastric drainage to assess total (enzymatic method) and single (high performance liquid chromatography) intragastric bile acids, and a gastroscopy with biopsies of the antrum and gastric body to assess histological damage to the mucosa. The results showed that there was a progressive increase in the fasting bile reflux of total bile acids with time (precholecystectomy median value 0.295 mumol/h; 6 months control median value 12.045 mumol/h; late control medial value 19.9 mumol/h; Friedman test, P = 0.0022). Examination of the gastric mucosa at the three moments of the study showed that histological damage worsened progressively. In fact chronic atrophic gastritis of the antrum was present in 10 percent of cases before surgery and in 50 percent 4 years after, and the prevalence of chronic superficial gastritis of the body progressed from 0 to 40 percent. Studies on larger groups of patients are necessary to evaluate whether these two phenomena are correlated.     

Short-term effects of bile diversion on postgastrectomy gastric histology

Twelve partially gastrectomized subjects who have consecutively undergone total biliary diversion for severe bilious vomiting were studied before and after operation in order to assess the effects of surgery on gastric histology and enterogastric reflux. Before and six months after operation, the following protocol was performed: (1) blood examinations including serum basal gastrin; (2) endoscopy with multiple gastric biopsies; and (3) quantitation of bile acids in the gastric aspirate. Of the preoperative symptoms, bilious vomiting and heartburn completely disappeared postoperatively in all the subjects. Fasting bile reflux was significantly reduced (bile reflux was annulled in six and considerably lowered in the remaining six subjects), and erythema of the gastric mucosa completely disappeared in all the subjects after diversion. Among histological findings, while a significant regression of foveolar hyperplasia was found both in the perianastomotic area and in the body of gastric remnant, none of the other aspects identifiable in postgastrectomy gastric mucosa (chronic gastritis changes included) were affected by diversion. These results show that biliary diversion is effective in correcting reflux, bilious vomiting, erythema, and foveolar hyperplasia of the gastric mucosa and confirm the suggested relationship between bile reflux and gastric foveolar hyperplasia.     

Characteristics of reflux gastritis

The amount of postprandial duodenogastric bile reflux was correlated with detailed histologic findings in the stomachs of 107 patients with dyspepsia. The reflux was associated with infiltration of mononuclear leukocytes, neutrophilic granulocytes, and eosinophilic granulocytes and with foveolar hyperplasia in the gastric mucosa. No significant association with intestinal metaplasia emerged. Our results suggest that postprandial duodenogastric bile reflux is characterized by superficial inflammatory changes in the gastric mucosa.     

Effect of biliary tract procedures on duodenogastric reflux and the gastric mucosa.

The effect of alterations in the biliary tract on the gastric milieu was evaluated in gallstone disease and after cholecystectomy or biliary fenestration and compared with a control group. Endoscopic bile reflux was often found in gallstone patients (67%) and almost always after cholecystectomy (89%). Gastric bile acid concentrations were greater in the gallstone patients than in the control patients, were higher still after cholecystectomy, and were highest after biliary fenestration. The pH of the gastric fluid was more alkaline in the cholecystectomized groups. Lysolecithin concentrations were generally low and did not differ between the groups, nor was there any difference in scintigraphic reflux between the groups. Endoscopic erythematous gastritis correlated with the grade of bile reflux and was a common finding after biliary tract procedures. There were no consistent histologic findings associated with duodenogastric reflux. Helicobacter pylori colonization rates were similar in the various patient groups and were not affected by the reflux grade.     

Duodenogastric reflux in chagas' disease

Increased duodenogastric reflux has been recognized as a cause of gastric mucosa damage. The frequent finding of bile-stained gastric juice and a suggested higher frequency of lesions of the gastric mucosa in patients with Chagas' disease, which is characterized by a marked reduction of myenteric neurons, suggest that impairment of intrinsic innervation of the gut might be associated with increased duodenogastric reflux. Duodenogastric bile reflux was quantified after intravenous injection of^99mtechnetium-HIDA, in 18 patients with chronic Chagas' disease, 12 controls, and 7 patients with Billroth II gastrectomy. All but one of the chagasic patients were submitted to upper digestive tract endoscopy. High reflux values (10%) were detected both in chagasic patients and in the controls, but the values for both groups were significantly lower (P< 0.01) than those obtained for Billroth II patients (median: 55.79%; range: 12.58– 87.22%). Reflux values tended to be higher in the Chagas' disease group (median: 8.20%; range: 0.0– 29.40%) than in the control group (median: 3.20%; range: 0.0– 30.64%), with no statistical difference between the two groups (P>0.10). Chronic gastritis was detected by endoscopy in 12 chagasic patients, benign gastric ulcer in 2 patients, and a pool of bile in the stomach in 11 patients. However, neither the occurrence of gastric lesions nor the finding of bile-stained gastric juice was associated with high reflux values after [^99mTc]HIDA injection. This study suggests that lesions of the intramural nervous system of the gut in Chagas' disease do not appear to be associated with abnormally increased duodenogastric reflux.     

Upper Gastrointestinal Findings in Chronic Renal Failure

Twenty-nine patients with chronic renal failure were examined both during the predialytic stage and after active treatment (dialysis, transplantation) for upper GI diseases. They underwent a gastric dose-response secretion test, gastroduodenoscopy, radiologic upper GI series, and fasting serum gastrin determination. Upper GI diseases increased in the active treatment stage. At the time of examination, patients with these diseases had a positive ulcer history, duodenitis, duodenogastric reflux, and blood group O more often in the predialytic stage. Their stimulation sensitivity to pentagastrin and their acid secretion capacity were greater, and they were less achlorhydric. Their fasting serum gastrin level was also lower. They had less endoscopically discovered gastritis, but microscopically, with regard to gastritis, they did not differ from those who did not develop upper GI complications. In conclusion, in chronic renal failure upper GI findings increase after the active treatment. Secretion tests and endoscopy performed before active treatment give an indication of those who will develop upper GI complications during active treatment.     

Upper gastrointestinal findings in chronic renal failure

Twenty-nine patients with chronic renal failure were examined both during the predialytic stage and after active treatment (dialysis, transplantation) for upper GI diseases. They underwent a gastric dose-response secretion test, gastroduodenoscopy, radiologic upper GI series, and fasting serum gastrin determination. Upper GI diseases increased in the active treatment stage. At the time of examination, patients with these diseases had a positive ulcer history, duodenitis, duodenogastric reflux, and blood group O more often in the predialytic stage. Their stimulation sensitivity to pentagastrin and their acid secretion capacity were greater, and they were less achlorhydric. Their fasting serum gastrin level was also lower. They had less endoscopically discovered gastritis, but microscopically, with regard to gastritis, they did not differ from those who did not develop upper GI complications. In conclusion, in chronic renal failure upper GI findings increase after the active treatment. Secretion tests and endoscopy performed before active treatment give an indication of those who will develop upper GI complications during active treatment.     

Effects of bile reflux on gastric mucosal lesions in patients with dyspepsia or chronic gastritis

AIM: To investigate the influences of bile reflux on profiles of gastric mucosal lesions in patients with dyspepsia or chronic gastritis. METHODS: A total of 49 patients diagnosed with dyspepsia and chronic gastritis underwent 24-h ambulatory and simultaneous monitoring of intragastric bilirubin absorbance and pH values, and then they were divided into bile reflux positive group and bile reflux negative group. Severity of pathological changes in gastric mucosa including active inflammation, chronic inflammation, intestinal metaplasia, atrophy and dysplasia as well as Helicobacter pylori (H pylori) infection at the corpus, incisura and antrum were determined respectively according to update Sydney system criteria. The profiles of gastric mucosal lesions in the two groups were compared, and correlations between time-percentage of gastric bilirubin absorbance >0.14 and severity of gastric mucosal lesions as well as time-percentage of gastric pH >4 were analyzed respectively. RESULTS: Thirty-eight patients (21 men and 17 women, mean age 44.2 years, range 25-61 years) were found existing with bile reflux (gastric bilirubin absorbance >0.14) and 11 patients (7 men and 4 women, mean age 46.2 years, range 29-54 years) were bile reflux negative. In dyspepsia patients with bile reflux, the mucosal lesions such as active inflammation, chronic inflammation, intestinal metaplasia, atrophy or H pylori infection in the whole stomach, especially in the corpus and incisura, were significantly more severe than those in dyspepsia patients without bile reflux. Moreover, the bile reflux time was well correlated with the severity of pathological changes of gastric mucosa as well as H pylori colonization in the near-end stomach, especially in the corpus region. No relevance was found between the time of bile reflux and pH >4 in gastric cavity. CONCLUSION: Bile reflux contributes a lot to mucosal lesions in the whole stomach, may facilitate H pylori colonization in the corpus region, and has no influence on acid-exposing status of gastric mucosa in patients with dyspepsia or chronic gastritis.     

Gastric mucosa in female patients with fundic glandular polyps.

To evaluate the characteristics of the gastric mucosa in women with fundic glandular polyps, we examined gastric acid secretion, fasting serum levels of pepsinogen I and gastrin, and gastric histology in 11 female patients with fundic polyps, and compared the results with 30 female controls without endoscopic abnormalities and 50 female patients with gastric foveolar hyperplastic polyps. No significant difference was found in gastric and secretion and fasting serum levels of pepsinogen I and gastrin between the patients with fundic glandular polyps and the control subjects. Histological examination showed that atrophic gastritis was generally not found in the patients with fundic glandular polyps. In contrast, gastric acid secretion and fasting serum levels of pepsinogen I were significantly lower and serum gastrin levels were significantly higher in the patients with foveolar hyperplastic polyps than in the other two groups. Also, patients with foveolar hyperplastic polyps had a higher prevalence and further advanced atrophic gastritis in the fundus than did the other two groups. Our investigations demonstrated that fundic glandular polyps arise from gastric mucosa without atrophic gastritis, whereas foveolar hyperplastic polyps develop from mucosa affected by atrophic gastritis, especially type A gastritis.     

Campylobacter-like organisms and gastritis: histopathology, bile reflux, and gastric fluid composition

We studied a prospective series of 107 randomly chosen dyspepsia patients without gastric ulcer for the association of spiral Campylobacter-like organisms (CLO) with features of antral and fundal gastritis and duodenogastric reflux. CLO were observed in 38% of the patients. The scores for all classes of inflammatory cells in both antral and body mucosa were significantly higher in the CLO-positive patients than in the CLO-negative ones (p less than 0.001), and foveolar hyperplasia was also associated with CLO (p less than 0.05). Metaplasia and glandular atrophy in the antral mucosa were significantly commoner in the CLO-positive group (p less than 0.05 and p less than 0.01, respectively). The body gastritis score correlated significantly with age in the CLO-negative patients (R = 0.33, p less than 0.01) but not in the CLO-positive ones. There were no significant differences between the groups with regard to duodenogastric reflux or intragastric pH. The results confirm that CLO are associated with gastritis, most notably superficial gastritis in the body and atrophic gastritis in the antrum, but their aetiological significance remains to be proved.     

Interrelationships among gastric mucosal morphology,secretion, and motility in peptic ulcer disease

Pathophysiologic abnormalities associated with ulcer disease include gastritis (particularly of the antral mucosa), excessive duodenogastric reflux, and altered motor activity of the stomach. It is not known whether these abnormalities are interrelated and whether they occur during periods of ulcer inactivity. We have tested the hypothesis that the morphological abnormalities of the gastric mucosa in inactive ulcer disease are proportional to an alteration of the gastric luminal milieu itself due to abnormal secretory and motor function. Thus, multiple endoscopic biopsies and 24-hr physiologic measurements were performed in 12 patients with well-documented ulcers in the past (seven type I gastric ulcer patients, five duodenal ulcer patients), now clinically and endoscopically in remission. Seven healthy individuals underwent similar studies and served as controls. Histologic quantification of inflammation and metaplasia (expressed as a gastritis index) was found to be significantly different among groups (P<0.01). Gastric ulcer patients exhibited a higher gastritis index than controls, while duodenal ulcer patients were intermediate. A significant inverse relationship was found between gastritis index and postprandial motility index (R ²=0.59,P<0.01) and a nonsignificant trend between gastritis index and fasting motility index. There was no difference among groups or detectable associations between gastritis index and intragastric pH or bile acid concentration. We conclude that gastric mucosal disease, expressed as gastritis index, persists during inactive ulcer disease. There is an association with antral hypomotility, which is more strongly manifested postprandially. It is not associated with gastric pH or bile acid concentration. Gastric mucosal inflammation and antral hypomotility predispose to ulceration rather than simply accompanying it.This work was supported in part by grant AM 26428 from the National Institutes of Health.     

Bile salts in the esophagus of patients with esophagitis

It is controversial whether bile salts are important in the pathogenesis of esophagitis. By sampling esophageal contents during ambulatory 24-h pH-monitoring we found that in a group of 18 patients with esophagitis all but 1 had detectable concentrations of bile salts in their esophagus. The concentrations of bile salts were low, however, and similar to those found in the gastric juice of 10 normal controls. It is concluded that bile salts are present in the esophagus of patients with esophagitis and that their presence results from duodenogastric reflux. The role of these refluxed bile salts in the pathogenesis of esophagitis is, however, unclear.     

Hypergastrinemia after Helicobacter pylori infection is associated with bacterial load and related inflammation of the oxyntic corpus mucosa

BACKGROUND AND AIM: Helicobacter pylori infection causes hypergastrinemia. This study aimed to determine the association between serum gastrin and the severity of H. pylori-related gastric histology. METHODS: A total of 458 dyspeptic patients were included in this study after the absence of gastric malignancy was confirmed using endoscopy. The gastric specimens of each patient were collected from the antrum and corpus for the analysis of H. pylori-related histology changes by updated Sydney's system. Before endoscopy, the fasting blood samples were collected for gastrin analysis. RESULTS: The H. pylori-infected patients had higher gastrin levels than those without infection (P = 0.01). Gastrin levels were related to H. pylori density and acute and chronic inflammation scores in the corpus mucosa (P < 0.05), but not in the antral mucosa (P = NS). Gastrin levels were also not related to the presence of gastric atrophy. Multivariate regression showed that the gastrin level was only related to acute corpus inflammation. However, in the patients without infection, the gastrin level was also associated with acute corpus inflammation. Nevertheless, the patients with denser H. pylori infection were more likely to have acute corpus gastritis than those with lighter H. pylori infection, and thus presented with higher gastrin levels (P < 0.05). CONCLUSIONS: The increased level of gastrin of serum after H. pylori infection was associated with acute inflammation in the gastric corpus mucosa, but not in the antral mucosa. Denser H. pylori infection causes more severe corpus gastritis and thus may lead to a higher fasting level of gastrin of serum.     

Antral Gastrin Cells and Serum Gastrin in Achlorhydria

Forty-five patients with achlorhydria due to severe atrophic corpus gastritis or gastric atrophy were studied by determination of serum gastrin, histological examination of multiple biopsy specimens from the antrum, and quantitation of gastrin cells revealed by an indirect immunofluorescence technique. In a reference group of 12 persons with normal gastric secretion and without atrophic antral gastritis, the mean number of gastrin cells per field of vision was 52±6.5 (S.E.M.). In a group of achlorhydric patients having normal antral mucosa (n = 24), the serum gastrin level was 324±56 pmol/1 and the number of gastrin cells was 79.6±7.5 cells/field of vision. The corresponding values for a group of achlorhydric patients with chronic superficial antral gastritis (n = 11) were 361±186 pmol/1 and 88.0±14.4 cells/field of vision. In a group of achlorhydric patients with atrophic antral gastritis (n = 10) serum gastrin was 15.0±3.3 pmol/1, and the number of gastrin cells was 6.2±3.3 cells/field of vision. Compared to the subjects in the reference group, the number of gastrin cells was significantly higher in the groups of achlorhydric patients with normal or superficially inflamed antral mucosa and significantly lower in achlorhydric patients with atrophic antral gastritis. It is concluded that serum gastrin in general is a good indicator for the presence or absence of antral atrophic gastritis in achlorhydria.