[Functional state of the hepatobiliary system in gastric and duodenal peptic ulcer].
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Cysteamine and propionitrile are members of a family of compounds which induce the formation of acute duodenal ulcers in fasted and fed rats. Gastric acid secretion is increased by both agents, and acid hypersecretion appears to be required for ulcer formation. To determine the role of gastrin in the ulcerogenic mechanism, cysteamine and propionitrile were administered to fasted rats and their effect on fasting and food-stimulated serum gastrin levels was studied. Intragastric administration of cysteamine caused a 3- to 4-fold increase in fasting serum gastrin levels over the values of controls. Propionitrile was a less effective stimulant of gastrin release, causing a 1.5- to 2-fold increase in gastrin levels over matched control rats. The food-stimulated rise in serum gastrin levels after either a chow meal or intragastric instillation of a peptone solution was markedly enhanced by cysteamine pretreatment. Three hours after feeding the serum gastrin levels of cysteamine pretreated rats were 6 times higher than those of fed controls. The high serum gastrin levels of cysteamine-pretreated fed rats could not be explained solely by the additive effects of cysteamine and food, indicating that a potentiating interaction may exist between the two stimulants of gastrin release. The importance of this drug-induced stimulation of gastrin release, under both fasted and fed conditions, in the ulcerogenic process has yet to be ascertained.
BACKGROUND: Because fewer than 1000 cases of primary adenocarcinoma of the duodenum have been reported, earlier series are limited by local referral patterns and the long periods of time needed for retrospective reviews. METHODS: This study reports the outcomes of preiampullary duodenal adenocarcinoma treatments in all hospitals of the Department of Veterans Affairs from 1987 through 1991, using computer and tumor registry records. Patients were grouped by their most aggressive treatment (resection > operative bypass > percutaneous biliary intubation) and survival calculated from the date of this procedure. RESULTS: Of 2185 patients with periampullary cancers (1753 pancreatic, 432 other periampullary), 85 were duodenal and thus comprised only 4% of periampullary tumors. Thirty-four duodenal cancers were resected, 44 bypassed, and 7 had biliary intubation, with 30-day mortality rates of 6%, 18%, and 0%, respectively. Mean survival exceeded 1 year in all groups, and resection resulted in a significant increase in mean survival (784 vs. 438 days for nonresection, P = 0.01). The projected 5-year survival rate after resection was 23%. Mean survival after resection of 9 Stage I-II cancers was 668 days, but was similar after 5 resections with nodal or other metastases. Similarly, survival did not correlate with cancer stage in 13 palliated patients. CONCLUSIONS: This large study of patients with duodenal cancer provides a unique perspective of disease prevalence and response to surgical treatment. Prolonged survival is common with any treatment, but the longest survivals were after resection.
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The stomachs of 8 healthy volunteers were intubated with a Levine tube under radiological control. In addition, a thin polyethylene tube was placed in the proximal duodenum. After a 1-hour period with no perfusion, the duodenum was perfused for two hours with 15% liver extract (LE) (pH 4.5--5.5; 1027 mosm/kg water) at a rate of 100 ml/hour either alone or in combination with intravenous infusion of different doses of exogenous pentagastrin. All subjects were also tested with the tubes in place for 3 hours, but with no perfusion or pentagastrin. Reflux to the stomach was monitored by addition of radioactive B12 to the perfusates. Plasma gastrin, gastric acid, and pepsin were measured in 15-minute periods. During perfusion of the proximal duodenum, where reflux of the perfusates was less than 4%, only a slight and inconstant change in plasma gastrin was seen. Gastric acid and pepsin outputs were increased to approx. 18% and 25% of the maximal pentagastrin stimulation respectively. Whereas 15% LE was shown to release gastrin by antral perfusion however, such release was not found by duodenal perfusion, except where reflux to the antrum was seen. The results suggest that intestinal stimulation of gastric secretion exists, but has not been found to be gastrin dependent in the present investigation.
Important abnormalities of the distal duodenum can be missed on the usual enteroclysis examination because of placement of the intubation tube beyond the ligament of Treitz. This can be avoided by extending the examination to include visualization of the duodenum during withdrawal of the nasojejunal tube. On the basis of the case reported here this procedure is suggested for patients with unexplained upper gastrointestinal bleeding in whom the remainder of the small bowel is normal.
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We have evaluated the effects of porcine pancreatic extracts on human pancreatic secretion. Ten male volunteers were intubated with a 4-lumen jejunal tube to collect gastric and duodenal secretions separately via the first and third tube, to infuse PEG 4000 distal the pylorus via the second tube and to apply porcine pancreatic extracts via the fourth tube distal the ligament of Treitz. Pancreatic extracts were given four times at 40 minute intervals; the first two as active enzymes and subsequently as heat denatured proportions. Secretin was continuously infused intravenously (0.5 E/kg bw/h) to achieve minimal pancreatic flow. Lipase, amylase, trypsin, chymotrypsin, volume, and bicarbonate were measured in duodenal contents in eight pooled 15 minute fractions. Three subjects who received HEPES-Ringer buffer instead of pancreatic enzymes served as controls. Plasma cholecystokinin (CCK) was measured using a sensitive bioassay. Both active and heat denatured pancreatic extracts caused a small but significant increase in amylase and chymotrypsin secretion. Basal plasma CCK values were 0.85 (0.05) pM. After intrajejunal instillation of either active or heat denatured pancreatic extracts plasma CCK rose to 3.25 (0.30) pM and to 3.28 (0.36) pM respectively. In a second group of five volunteers, plasma CCK concentrations were measured after a test meal. On day 1, volunteers received a liquid fat and protein rich meal and on day 2, the same test meal containing porcine pancreatic extracts. In both cases, a similar increase in plasma CCK was observed. We conclude that therapy with pancreatic extracts stimulate pancreatic enzyme secretion. This may be mediated through release of CCK.
Malabsorption of bile acids is known to occur in patients with pancreatic insufficiency particularly when due to cystic fibrosis. Abnormal biliary secretion or intraluminal acidic precipitation of bile acids could contribute to the steatorrhea of pancreatic insufficiency. To measure bile acid outputs and duodenal concentrations of bile salts and lipids simultaneously, we performed intestinal intubation and perfusion studies during feeding of a solid test meal in 6 healthy controls and 8 adult patients with advanced acquired exocrine pancreatic insufficiency. The effects of various treatment regimens were also investigated. Postprandial bile acid secretion was similar in all treatment groups. However, significant (P less than 0.05) reductions in micellar concentrations of bile acids and fatty acids were observed in untreated pancreatic insufficiency. These abnormalities were directly related to pH-induced precipitation of bile acids and were corrected only by the addition of cimetidine to standard pancreatin therapy. Thus, in pancreatic insufficiency, treatment with pancreatin plus cimetidine enhances fat digestion and absorption by reducing both acid-peptic inactivation of lipase and acidic precipitation of bile acids.
A retrospective analysis of 18 cases of duodenal trauma is presented. Perforations (in 10 cases) were sutured in two layers, using absorbable material, and intramural hematomas (8 cases) were left to resolve spontaneously. Nasogastric intubation was the only method of intestinal decompression, and was used in both patient groups. There were no direct duodenal complications. The mean hospital stay was 14 days. Primary repair with absorbable sutures combined with a few days of nasogastric decompression seems to be a safe and adequate method of managing uncomplicated duodenal perforations. Intramural duodenal hematomas need no intervention except nasogastric decompression.
Endoscopic duodenal biopsies were taken from 27 patients with suspected coeliac disease and compared with intubation capsule jejunal biopsies. The specimens were reported without knowledge of the patients' names or symptoms. In 24 patients (89%), coeliac disease could either be diagnosed or excluded with 100% accuracy, despite the inability to orientate the biopsies correctly. Six biopsies were considered technically unsatisfactory, but only in three (11%) was it impossible to exclude coeliac disease. Duodenal biopsies were also taken from 118 consecutive patients attending for routine upper gastrointestinal endoscopy, and 1 patient with coeliac disease was discovered. We conclude that endoscopic duodenal biopsies are a reliable and worthwhile screening test for coeliac disease in certain patients attending for routine upper gastrointestinal endoscopy.
Although abdominal complaints are frequent in both acute and chronic alcoholism, little is known of the effect of ingestion of ethanol with a meal on the function of the upper digestive tract. We have studied the effects of oral ethanol (1 g/kg body wt) taken with food on the gastric emptying rate of a solid-liquid meal as measured by a dual radioisotope technique in six normal subjects; and the gastric response (emptying and secretion), biliopancreatic secretions, and duodenal nutrient absorption after an homogenized meal, as evaluated by a gastroduodenal intubation-marker perfusion technique on seven healthy volunteers. In the latter experiments, radioimmunoassays of gastrin, secretin, cholecystokinin, pancreatic polypeptide, motilin, somatostatin, gastric inhibitory polypeptide, and vasoactive intestinal polypeptide were performed serially. As compared with the control experiment, alcohol induced the following effects: marked delay of gastric emptying of solids, smaller slowing effect on gastric emptying of the liquid phase of the solid-liquid meal and of the homogenized meal; no significant change in gastric acid secretion; no change in the overall postprandial pancreatic enzyme outputs, but a delay of lipase secretion; no change in the early bile salt postprandial output, but a reduced bile salt secretion from the second postprandial hour onwards; no significant change in carbohydrate and lipid duodenal absorption; and a significantly greater postcibal gastrin release. The mechanisms for these effects of alcohol on upper digestive tract function remain to be clarified.
The clinical features and surgical management of two patients with primary adenocarcinoma of the bile duct in association with familial polyposis coli are described. The first patient had had subtotal colectomy for familial polyposis coli, and several resections of duodenal tumors. Carcinoma developed in the common bile duct and was treated with intubation and radiation therapy; he is still alive 2 years later. A second patient with cancer at the bifurcation of the bile ducts was treated with intubation and radiotherapy; 1 year later she had intestinal hemorrhage from a sigmoid colon cancer, and multiple colonic polyps were noted. We believe that this is the first report in the English literature of biliary cancer in association with familial polyposis coli or Gardner's syndrome.
Duodenal mucosal bicarbonate secretion (DMBS) prevents acid-peptic damage and facilitates nutrient absorption. DMBS is diminished in patients with duodenal ulcers and is normalized after Helicobacter pylori eradication. The measurement of DMBS in human patients in vivo requires intubation with a multi-lumen balloon tube and permits limited testing with putative agonists and antagonists. Our purpose was to develop a means to investigate transport events in human duodenal biopsy samples in vitro. After validation studies in a modified mini-Ussing chamber were performed, duodenal transport events were examined in proximal endoscopic biopsy samples from normal volunteers (n = 17). Tissues were mounted in modified mini-Ussing chambers (volume 2.5 ml, surface area 3.8 mm2). Short circuit current (Isc), potential difference (PD), and bicarbonate secretion were determined under basal conditions and after stimulation with graded doses of prostaglandin E2 (PGE2)(10(-8) to 10(-4) mol/L) and dibutyryl cAMP (db-cAMP)(10(-4) to 10(-2) mol/L). Duodenal tissues remained viable for at least 2 hours and exhibited stable basal HCO3(-) secretion and electrical parameters. Stimulation with PGE2 and db-cAMP resulted in dose-related increases in both Isc and HCO3(-) secretion (P < .05) that were abolished by ouabain and anoxia. It is concluded (1) that human duodenal bulb biopsy samples maintain their inherent transport function in mini-Ussing chambers and (2) that by using this novel method it will be possible to define the transport events that modulate human duodenal secretion, in particular bicarbonate secretion, in both health and disease.
We performed a prospective, randomized, double-blind study to assess the efficacy of topical prostaglandin E2 (PGE2) in altering the course of patients with severe upper gastrointestinal tract hemorrhage. Forty-four patients with life-threatening, endoscopically proven hemorrhage were randomly allocated to receive either PGE2 or placebo for seven days. Severity of mucosal injury, determined by endoscopy, was scored both before and after completion of treatment. There were no significant differences between groups in either transfusion requirements or successful outcomes. However, the PGE2 group had significantly improved endoscopic injury scores while the placebo group did not. Therefore, topical PGE2 does not control acute hemorrhage from established upper gastrointestinal tract lesions, but it does result in an accelerated healing of established lesions.
BACKGROUND: Sufficient intraluminal concentrations of 5-aminosalicylic acid (ASA) within inflamed regions of the intestine are required for therapeutic efficacy in inflammatory bowel disease. Various oral delayed release preparations have been developed to ensure that 5-ASA is set free in those parts of the gut, which are most frequently affected. However, resulting intraluminal concentrations within the small bowel are unknown. Therefore, we determined and compared 5-ASA release within different segments of the small bowel from an Eudragit L coated 5-ASA preparation (Salofalk) and from an ethylcellulose coated microsphere preparation (Pentasa). METHODS: Twelve healthy subjects were intubated with an oro-ileal multilumen-tube for marker perfusion, duodenal, jejunal and ileal aspiration of chyme and intestinal manometry. Each subject received 500 mg 5-ASA (Salofalk, n = 6, or Pentasa, n = 6) together with a semiliquid test meal. Intestinal aspirates, blood and urine samples were obtained in regular intervals for 7 to 10 hours and were analysed for 5-ASA and its main metabolite acetyl-5-ASA by HPLC. RESULTS: With Salofalk, gastric emptying of 5-ASA did not take place in the digestive, but in the subsequent interdigestive period. Luminal delivery of 5-ASA and acetyl-5-ASA increased from the duodenum (3% of dose) to the ileum (30% of dose). 10% of the dose administered were excreted in urine and about 90% reached the colon unreleased or solubilised. By contrast, with Pentasa, 5-ASA was delivered to the duodenum together with the test meal and released continuously throughout the small intestine (about 20% of dose solubilised at each intestinal site). Only 3.5% of the dose administered were excreted in urine. Deliver of 5-ASA to the colon was equal to Salofalk. CONCLUSIONS: From both preparations, considerable amounts of 5-ASA are released during small intestinal transit thus explaining therapeutic efficacy in small intestinal Crohn's disease. Because of specific release patterns, Salofalk may be of use especially in terminal ileal disease, where as patients with extensive small intestinal disease including the proximal small intestine might benefit from Pentasa.