cholecystokinin and Bile-Duct-Neoplasms

The aim of this study was to examine whether the type of bilioenterostomy enhances biliary carcinogenesis in the hamster model. Syrian hamsters were divided into the following groups; simple laparotomy (control group), cholecystoduodenostomy with dissection of the extrahepatic bile duct on the distal end of the common duct (CDDB group) and cholecystoileostomy with dissection of the extrahepatic bile duct on the distal end of the common duct (CIDB group). Following these procedures, all hamsters received N-nitrosobis(2-oxopropyl)amine. The diameter of the extrahepatic bile duct and plasma levels of cholecystokinin (CCK) were measured and the number of neoplastic lesions was counted microscopically. Proliferative effect of the procedures on the biliary epithelium was examined by proliferative cell nuclear antigen. In the CDDB group the extrahepatic bile duct was significantly dilated and carcinogenesis of the gall-bladder and extrahepatic bile ducts was enhanced. In the CIDB group the CCK bioactivity was stimulated and intrahepatic biliary duct, but not gall bladder and extrahepatic bile duct, carcinogenesis was promoted more than that observed in the CDDB group. Proliferation of the biliary duct epithelium was enhanced in both the CDDB and CIDB groups. Cholecystoduodenostomy enhanced intra- and extrahepatic bile duct carcinoma, whereas cholecystoileostomy promoted only intrahepatic bile duct carcinoma. Some factors in the intestinal juice seem to play a role in the promotion of biliary tract carcinoma.

Topics: Animals; Bile Duct Neoplasms; Bile Ducts; Bile Ducts, Extrahepatic; Biliary Tract; Biliary Tract Neoplasms; Carcinogens; Carcinoma, Papillary; Cell Division; Cholecystokinin; Cricetinae; Epithelium; Female; Gallbladder; Gallbladder Neoplasms; Ileum; Mesocricetus; Nitrosamines; Proliferating Cell Nuclear Antigen

The influences of (a) intraluminal bile deficiency due to common bile duct obstruction and (b) intraduodenal administration of pooled own bile and bovine trypsin on the plasma cholecystokinin (CCK) response to oral fat (Lipomul) ingestion were investigated in seven patients with periampullary tumors and 10 healthy volunteers. Basal and fat-stimulated plasma CCK levels in the patients were significantly higher than in the normal controls. Intraduodenal administration of pooled own bile at a rate of 100 ml/h significantly suppressed both basal and fat-stimulated CCK secretion. Simultaneous administration of pooled own bile (100 ml/hr) and bovine trypsin (600 mg/hr) caused further significant suppression of fat-stimulated CCK secretion compared with that under bile infusion alone. These results indicate that both intraluminal bile and trypsin exert a negative feedback effect on the release of CCK in humans.

Topics: Aged; Bile; Bile Duct Neoplasms; Carcinoma; Cholecystokinin; Cholestasis; Dietary Fats; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Trypsin

The role of intraduodenal bile in regulation of plasma cholecystokinin (CCK) levels were investigated in patients with obstructive jaundice under external bile diversion and under physiological bile flow into the duodenum by internal bile drainage. Basal plasma CCK levels determined by a specific and sensitive bioassay in patients under external bile drainage (2.2 +/- 0.2 pmol/liter; mean +/- SE) were significantly higher than those in control subjects (1.0 +/- 0.3 pmol/liter). In control subjects, the peak CCK response (6.2 +/- 0.7 pmol/liter) to a test meal was seen at 45 min, whereas that in patients under external bile drainage, it was seen at 20 min after a test meal (17.6 +/- 3.2 pmol/liter; P < 0.01 vs controls). After peak response, plasma CCK levels in controls gradually decreased, but remained significantly elevated during a 3-hr observation period. In patients under bile diversion, the test meal caused a prompt plasma CCK peak, with a transient fall followed by a continuous rise until 180 min postprandially. In six patients, external bile diversion was changed to internal biliary drainage with a stent tube within two weeks to maintain physiological bile flow into the duodenum. Internal bile drainage normalized basal (0.9 +/- 0.2 pmol/liter) as well as meal-stimulated CCK release (peak value: 5.0 +/- 0.8 pmol/liter). These results demonstrate that endogenous bile exerts tonic inhibition on basal and postprandial plasma CCK levels in humans.

Topics: Adenoma, Bile Duct; Adult; Aged; Ampulla of Vater; Bile; Bile Duct Neoplasms; Cholecystokinin; Cholestasis; Common Bile Duct Neoplasms; Drainage; Eating; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Time Factors

Exogenous administration of cholecystokinin (CCK) or caerulein inhibits growth of SLU-132, a human cholangiocarcinoma that we have shown to possess receptors for CCK. Chronic administration of cholestyramine, a resin that binds bile salts, increases release of CCK and growth of the pancreas in guinea pigs. Feeding the bile salt, taurocholate, inhibits meal-stimulated release of CCK. The purpose of this study was to determine whether endogenous CCK affects growth of the human cholangiocarcinoma, SLU-132. We implanted SLU-132 subcutaneously into athymic nude mice. The bile salt pool was depleted by feeding 4% cholestyramine for 40 days, either alone or enriched with 0.5% taurocholate for 32 days. When the mice were killed, tumors and pancreas were removed. Cholestyramine significantly inhibited the growth of SLU-132 and stimulated growth of the normal pancreas. Feeding of taurocholate acted to stimulate tumor growth. These results demonstrate that endogenous levels of CCK regulate growth of this human cholangiocarcinoma. Our findings suggest that manipulation of levels of endogenous gut hormones may, in the future, play a role in management of patients with certain gastrointestinal cancers.

Topics: Adenoma, Bile Duct; Animals; Bile Duct Neoplasms; Cholecystokinin; Cholestyramine Resin; Diet; DNA; Humans; Male; Mice; Mice, Nude; Neoplasm Transplantation; Organ Size; Pancreas; RNA; Taurocholic Acid

Gastrointestinal polypeptide hormones regulate growth of various normal gastrointestinal tissues as well as certain visceral cancers. Since cholecystokinin (CCK) promotes growth of normal biliary tract, we sought to determine whether CCK affects the growth and metabolism of human cholangiocarcinoma line SLU 132. Twenty-six nude mice with s.c. xenografts of this cancer received either CCK octapeptide (50 micrograms/kg/dose) or 0.9% NaCl solution (saline) twice a day i.p. for 14 days. Tumor volume was calculated from Vernier caliper measurements. At sacrifice on Day 15, tumors were excised, weighed, and examined histologically. DNA, RNA, and protein were measured in the xenografted carcinomas. Because this cholangiocarcinoma produces carcinoembryonic antigen (CEA), we obtained serum at sacrifice for CEA radioimmunoassay and also tumor tissue for CEA immunolabeling with murine anti-CEA monoclonal antibody. Serum CEA levels were 90% higher in the CCK-treated group. Tumor tissue in the CCK-treated group also contained more CEA than did the controls. Mean tumor volume increased significantly in the saline group during the 14-day treatment period, whereas mean tumor volume did not increase significantly in the CCK group. Exogenous high-dose CCK thus appears to increase production and release of CEA from SLU-132; it also appears to retard growth of this tumor line in the nude mouse.

Topics: Adenoma, Bile Duct; Aged; Animals; Bile Duct Neoplasms; Body Weight; Carcinoembryonic Antigen; Cholecystokinin; Humans; Male; Mice; Mice, Nude; Neoplasm Transplantation; Transplantation, Heterologous

CEA concentration in juice collected during the Secretin-Pancreozymin test, and cytology were evaluated in order to establish whether they may be used as an aid in the diagnosis of pancreatic carcinoma before resorting to x-ray examinations. Thirty-three subjects were studied: 6 normal subjects, 12 with chronic pancreatitis, 3 after recovery from acute pancreatitis, 8 with gall-stones, 3 with carcinoma of the pancreas and 1 with cancer of the biliary tract. Three duodenal juice samples (at 30, 60 and 90 mins of hormonal infusion) were taken in each subject for CEA, cytology, bicarbonate and trypsin determinations. Although a significant statistical difference was noted between normal subjects and patients with carcinoma of the pancreas in the 30-min-juice sample, CEA concentration in the duodenal juice did not seem a reliable index in the diagnosis of pancreatic carcinoma. The information provided by cytology was also very scanty and sometimes misleading. The clinical picture and radiological investigation still remain the surest basis for the diagnosis of pancreatic cancer.

Topics: Adult; Bile Duct Neoplasms; Carcinoembryonic Antigen; Cholecystokinin; Cholelithiasis; Female; Humans; Male; Middle Aged; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis; Secretin

Topics: Angiography; Bile Duct Neoplasms; Celiac Artery; Cholecystokinin; Gallbladder Neoplasms; Hepatic Artery; Humans; Mesenteric Arteries; Pancreatic Neoplasms

Topics: Aged; Ampulla of Vater; Bile Duct Neoplasms; Cholecystokinin; Diverticulum; Duodenal Diseases; Duodenal Ulcer; Duodenum; Endoscopes; Endoscopy; Humans; Intestinal Polyps; Intubation, Gastrointestinal; Male; Methods; Optics and Photonics; Time Factors

Topics: Adolescent; Adult; Aged; Amylases; Bicarbonates; Bile Duct Neoplasms; Biliary Tract Diseases; Bilirubin; Celiac Disease; Cholecystokinin; Diagnosis, Differential; Duodenum; Female; Hemochromatosis; Humans; Hydrogen-Ion Concentration; Intestinal Secretions; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Pancreatitis; Protein-Losing Enteropathies; Secretin

Topics: Bicarbonates; Bile Duct Neoplasms; Biliary Tract; Biliary Tract Diseases; Biomedical Research; Cell Biology; Cholecystokinin; Disease; Duodenal Neoplasms; Humans; Pancreas; Pancreatic Neoplasms; Pancreatitis; Pharmacology; Secretin

Topics: Bile Duct Neoplasms; Bile Ducts; Cholecystokinin; Gastrointestinal Hormones; Humans; Pancreas; Pancreatic Neoplasms; Secretin