(1/85) Duodenogastric reflux: clinical and therapeutic aspects.
BACKGROUND: Duodenogastric reflux is believed to cause damage to gastric mucosa. Most reports on this disorder concern adult patients. PATIENTS AND METHODS: 1120 children with abdominal pain were studied; endoscopic features of duodenogastric reflux were found in 92 patients. To confirm the diagnosis of duodenogastric reflux, cholescintigraphy (Tc99-HEPIDA) was performed. Children with confirmed duodenogastric reflux by scintigraphy were given a prokinetic drug (cisapride). RESULTS: Endoscopic features of duodenogastric reflux were found in 92 children; the diagnosis was confirmed by scintigraphy in 59 patients. There was no significant difference in the severity of inflammation in gastric mucosa compared with the control group, whereas significantly fewer of these patients were infected with Helicobacter pylori. There was no correlation between regions of isotope accumulation and inflammatory lesions in the stomach. The prokinetic drug (cisapride) helped eliminate or greatly reduce duodenogastric reflux in children. CONCLUSIONS: When endoscopic features of duodenogastric reflux are found the final diagnosis should be based on an examination that does not itself influence the motility of the gastrointestinal tract: cholescintigraphy seems to be a useful method. However, because the use of milk as a test meal affects the scintigraphic image, there was no correlation between the area of isotope accumulation and the localisation of inflammatory lesions in the stomach. Duodenogastric reflux seems to be less important as a cause of inflammatory lesions than other factors (such as genetic predisposition, stress, etc). Prokinetic drugs have a beneficial influence on treatment results in children with inflammatory lesions of gastric mucosa with duodenogastric reflux. (+info)
(2/85) Enterogastric reflux mimicking gallbladder disease: detection, quantitation and potential significance.
OBJECTIVE: Visualization of enterogastric reflux (EGR) may be present during hepatobiliary imaging. Reflux of bile may damage the gastric mucosa, altering its function, and cause such symptoms as epigastric pain, heartburn, nausea, intermittent vomiting and abdominal fullness. These symptoms also are associated with gallbladder disease. The aim of this study was to quantitate the EGR index (EGRI) and to determine if a difference exists in normal and abnormal responses using standard cholecystokinin (CCK)-augmented hepatobiliary imaging. METHODS: This study used 129 patients. LAO dynamic data on a 128 x 128 matrix at a rate of 1 frame/min were obtained. After the gallbladder ejection fraction (GBEF) was determined, the EGRI (%) was calculated by relating the counts in the gastric ROI to the counts in the hepatobiliary ROI at a specified time. The results were compared with the patient's final clinical diagnosis. RESULTS: Normal responders (GBEF > or = 35%) had a higher EGRI than abnormal responders with a P = 0.001 EGR observed in 75 patients (58.1%). Significant reflux (EGRI > or = 14.2% at 15 min) was observed in 29 additional patients (22.5%). Patients with EGRI > or = 24.5% showed a strong association with the pathophysiologic syndrome of gastritis, alkaline reflux, gastric ulcer and gastro esophageal reflux disease. There was no EGR observed in the remaining 25 patients (19.4%). CONCLUSION: This simple addition to the CCK-augmented hepatobiliary imaging may both detect and quantitate abnormal EGR as the cause of the patient's symptoms in the presence of a normal GBEF result, and/or those patients with risk factors for gastritis. (+info)
(3/85) Duodenal-content reflux esophagitis induces the development of glandular metaplasia and adenosquamous carcinoma in rats.
Recent studies have demonstrated that refluxed duodenal contents cause esophageal carcinoma in rats without exposure to carcinogens. The histopathological spectrum of these carcinomas includes squamous-cell carcinoma, adenocarcinoma and adenosquamous carcinoma. Pure adenocarcinomas are thought to arise in areas of columnar metaplasia adjacent to the anastomosis, similar to Barrett's esophagus in humans. In contrast, the histogenesis of adenosquamous carcinomas is unclear. The purpose here was to investigate the pathogenesis of esophageal adenosquamous carcinomas in a time-course experiment of chronic duodenal-content reflux without carcinogen. Forty-two 8-week-old male Sprague-Dawley rats were divided into seven groups and exposed to duodenal-content esophageal reflux during 10, 15, 20, 25, 30, 35 and 40 weeks, respectively. All animals underwent an esophagojejunostomy with gastric preservation in order to produce chronic esophagitis. The rats received a standard diet without addition of carcinogens. An increasing incidence of glandular metaplasia and carcinoma was observed over the time course, starting at 20 weeks. After 40 weeks of reflux, multiple foci of glandular metaplasia and adenosquamous carcinoma were found in 83 and 50% of the animals, respectively. Most of the carcinomas occurred in the middle and proximal esophagus and had a dual pattern of differentiation, glandular and squamous. These findings confirm that duodenal content reflux alone has a carcinogenic effect. We propose that chronic duodenal reflux induces the development of metaplastic cells with glandular differentiation from the stem cells of squamous epithelium, and that glandular metaplastic foci are the morphological element from which tumors with a dual pattern of differentiation arise. (+info)
(4/85) Duodenogastric reflux and foregut carcinogenesis: analysis of duodenal juice in a rodent model of cancer.
The incidence of esophageal adenocarcinoma is increasing rapidly. In rats, surgically induced duodenoesophageal reflux is carcinogenic. One proposed mechanism of carcinogenesis is based on the reaction of physiological bile acids with nitrite to produce carcinogenic N:-nitroso amides. To test this hypothesis, duodenal juice was analyzed for endogenously formed N:-nitroso bile acids and its genotoxicity was determined. Esophagojejunostomy was performed on 15 Sprague-Dawley rats to produce duodeno-esophageal reflux. At the time of surgery and 2 and 6 weeks later, duodenal contents were aspirated and analyzed immediately. High performance liquid chromatography coupled to tandem mass spectrometry was used to detect bile acids and their nitroso derivates. Genotoxicity was assessed using a micronucleus test. The characteristic pattern of bile acid derivatives, with taurocholic acid (TCA) and glycocholic acid (GCA) as the predominant conjugates, was detected in all samples. However, even selective reaction monitoring experiments failed to demonstrate the presence of any N:-nitroso-TCA or N:-nitroso-GCA. In addition, other nitroso derivatives could not be detected in any of the samples by neutral loss experiments monitoring the loss of nitric oxide (detection limit 0.1% of the concentration of TCA). All samples were cytotoxic, but neither the preoperative nor the postoperative samples were genotoxic. Duodenal juice was cytotoxic but not genotoxic. Tumorigenesis of esophageal adenocarcinoma in the rodent model could not be linked to a specific carcinogen, especially not to nitroso bile acids. Chronic inflammation is likely to be the mechanism of carcinogenesis by duodenogastric reflux. (+info)
(5/85) Expression of cyclin D1 and p53 and its correlation with proliferative activity in the spectrum of esophageal carcinomas induced after duodenal content reflux and 2,6-dimethylnitrosomorpholine administration in rats.
Alterations in expression of the p53 and cyclin D1 genes have been implicated in the development of esophageal carcinomas in both humans and animal models. We hypothesize that altered expression of cyclin D1 and p53 may be involved in the sequential development of esophageal carcinomas with glandular differentiation induced by the carcinogen, 2,6-dimethylnitrosomorpholine (DMNM) in rats with duodenal content reflux esophagitis. In the present study Sprague-Dawley rats were given DMNM 15 days after performing an esophago-jejunostomy in order to induce chronic duodenal content reflux esophagitis. Expression and localization of p53, cyclin D1 and Ki-67 were examined by immunohistochemical analyses. Twenty of 24 animals developed different types of esophageal carcinomas, including pure squamous carcinoma, adenosquamous carcinoma and pure adenocarcinoma. Undifferentiated basaloid areas were frequently observed in these tumors. Cyclin D1 overexpression was observed in hyperplastic lesions and increased through dysplasia and in undifferentiated areas of infiltrating carcinoma. Cyclin D1 expression coincided with increased Ki-67 expression and decreased along with cell differentiation. The p53 immunohistochemical pattern was parallel to that of cyclin D1, although the percentage of positive cells was usually smaller in all lesions and increased p53 expression started at the dysplastic stage. These findings suggest that overexpression of cyclin D1 may be an early event in DMNM-induced rat esophageal tumorigenesis, causing increased proliferation of esophageal stem cells. Abnormal p53 expression may then be required to promote the development of neoplastic transformation from dysplastic epithelium through invasive phenotype, being more evident in cancer cells with squamous differentiation. (+info)
(6/85) 24-hour gastroesophageal double pH monitoring acid and alkaline gastroesophageal and duodenogastric refluxes in pediatric patients.
OBJECTIVE: To study the pathophysiologic significance of gastroesophageal and duodenogastric-esophageal refluxes in pediatric patients. METHODS: Gastroesophageal double pH monitoring was performed on 68 children with gastroesophageal reflux (GER) diseases and 39 normal children. The pH shifts in the intra-gastric and esophageal lumina were recorded for a total of 24 hour period (P1) and for the period of gastric empty (P2) in supine and upright body postures. RESULTS: The following reflux types were identified: acid GER in 40 cases (58.8%), alkaline GER (AGER) in 8 cases (11.8%), mixed GER (MGER) in 14 cases (20.6%) and silent GER (SGER, i.e., reflux with normal pH values in P1) in 6 cases (8.8%) as well as duodenogastric reflux (DGR). The results showed a number of transient GER and DGR (19 of 39 children) in the control group, recorded mainly in the upright position at meal times and 2 hours postprandially. All pH variables for acid reflux were higher in the acid GER and MGER groups than those in the control group (P < 0.01). The alkaline episode was significantly noted in cases with AGER and MGER in the supine position during P2. There was no significant difference in terms of incidence of esophagitis between GER groups. The gastroesophageal double pH monitoring produces the higher positive diagnostic rate of 91.2% than single esophageal pH testing (79.4%). CONCLUSIONS: Transitory GER and DGR at meal times and 2 hours later might be a physiologic phenomenon. Acid and alkaline reflux occurring in the supine position during P2 should be considered of pathologic significance. This combined gastroesophageal pH monitoring is used not only to improve the diagnostic rate but also to guide clinicians to choose efficient anti-reflux therapy based on the type of reflux as well as to provide refined information for the further study of the pathophysiology of duodenogastroesophageal reflux. (+info)
(7/85) Inhibition of gastrointestinal lipolysis by Orlistat during digestion of test meals in healthy volunteers.
The inhibition of digestive lipases by the antiobesity drug Orlistat along with lipolysis levels and fecal fat excretion were measured in healthy humans. Orlistat was found to be a powerful gastric lipase inhibitor, achieving 46.6--91.4% enzyme inhibition and thus greatly reducing gastric lipolysis of solid and liquid meals (11--33% of respective controls). Gastric lipase inhibition by Orlistat was extremely fast (half-inhibition time < 1 min). Duodenal lipolysis was reduced significantly by Orlistat given with the solid meal (32.6--37.6% of controls) but was only slightly reduced by Orlistat given with the liquid meal (74.5--100% of controls). Human pancreatic lipase (HPL) inhibition was found to be high (51.2--82.6%), however, regardless of the meal. These paradoxical results were explained when in vitro lipolysis experiments were performed. The rates of HPL inhibition by Orlistat were found to be similar with both types of meals (half-inhibition time 5--6 min), but the preemulsified triglycerides of the liquid meal were rapidly hydrolyzed by HPL before the enzyme was significantly inhibited by Orlistat. With the solid meal, the rate of hydrolysis of the meal triglycerides by HPL was slower than the rate of HPL inhibition by Orlistat. As predicted from the previous results, the effects of Orlistat on fat excretion levels were found to be much greater with the solid (40.5--57.4% of ingested fat) than with the liquid (4.2--18.8%) test meal. (+info)
(8/85) Duodenogastric reflux following cholecystectomy in the dog: role of antroduodenal motor function.
BACKGROUND: Duodenogastric reflux has been implicated in the pathogenesis of gastric ulcer and gastritis. Duodenogastric reflux after cholecystectomy is also a possible cause of post-cholecystectomy syndrome. AIM: To investigate the role of antroduodenal motor function in increased duodenogastric reflux following cholecystectomy and the effect of trimebutine maleate (trimebutine) on the duodenogastric reflux in conscious dogs. METHODS: Antropyloric and duodenal motility and bile acids content in the gastric juice were measured for 3 h during the inter-digestive state in dogs with or without cholecystectomy. RESULTS: Bile acids content in the gastric juice of cholecystectomized dogs was significantly higher than that of non-cholecystectomized dogs. The frequency of pyloric relaxation during phase II of the migrating motor complex was significantly increased following cholecystectomy. Intravenous infusion of trimebutine inhibited both the increased duodenogastric reflux and the frequency of pyloric relaxation in the cholecystectomized dog. CONCLUSION: Duodenogastric reflux and frequency of pyloric relaxations were increased in cholecystectomized dogs and trimebutine suppressed both of them. These findings suggest that the increased frequency of pyloric relaxation contributes to the duodenogastric reflux following cholecystectomy. (+info)