Elevated levels of opioid growth factor in the plasma of patients with pancreatic cancer.

Opioid growth factor (OGF, [Met5]-enkephalin) is an endogenous peptide that regulates the growth of human pancreatic cancer. To evaluate whether human subjects with pancreatic cancer have alterations in plasma levels of OGF, fasting blood samples were obtained from 15 patients with histologically confirmed pancreatic adenocarcinoma. Forty-five subjects with other malignancies, 20 patients with acute pancreatitis, and 30 aged-matched patients without cancer served as control populations. Individuals with pancreatic cancer had OGF values, as determined by radioimmunoassay, that were up to 7.3-fold greater than control subjects. No differences were found between OGF values obtained from patients with other malignancies, acute pancreatitis, or subjects without cancer. The sensitivity and specificity of OGF for pancreatic cancer were greater than either CA 19-9 or CEA. These data indicate that pancreatic cancer is associated with a marked increase in plasma OGF levels and suggest that this peptide may serve as a useful diagnostic tool in the screening for this disease.

Acute right-lower-quadrant mass presenting after laparoscopic cholecystectomy.

Hernia formation at trocar sites has been reported following laparoscopic surgical procedures. We present a case, however, of a healthy woman with signs, symptoms, and physical findings consistent with an incarcerated inguinal hernia 3 days after an uneventful laparoscopic cholecystectomy. Exploratory laparotomy revealed a small bile leak from an accessory duct of Luschka but did not identify an intra-abdominal process responsible for the patient's symptoms. Following the exploration, it was felt that the patient's presentation was likely due to tracking of carbon dioxide and bile-stained irrigation fluid to the right lower quadrant from the lateral laparoscopic trocar sites.

Intracerebroventricular secretin enhances pancreatic volume and bicarbonate response in rats.

BACKGROUND: Although secretin has been found within the brain, its central role in pancreatic exocrine function has not been previously addressed. The hypothesis that intracerebroventricular secretin enhances pancreatic volume and bicarbonate output at doses that have no effect when given intravenously was tested. METHODS: Sprague-Dawley rats had a cannula stereotactically placed into the left lateral cerebral ventricle 24 hours before study. At laparotomy the bile and pancreatic ducts were separately cannulated and excluded for tared collections and bicarbonate assay. RESULTS: Increasing doses of intracerebroventricular secretin (0.005, 0.05, and 0.5 microgram/1.0 microliter) induced a significant dose-related increase in bicarbonate output (2.95, 3.32, and 4.02 microEq/30 min, respectively) above basal (2.62 microEq/30 min) compared with control or intracerebroventricular saline treated animals. Pancreatic volume increased to 59.7 microliters at the lowest intracerebroventricular dose and increased (p < 0.025) to 65.8 microliters at the 0.05 intracerebroventricular secretin dose when compared with basal (59.4 microliters). To show that this was not a systemic effect of secretin, intravenous infusion of secretin at 0.005 and 0.05 microgram/kg/hr failed to stimulate either volume or bicarbonate output compared with that observed with intracerebroventricular secretin over the same dose range. CONCLUSIONS: These observations indicate that intracerebroventricular secretin stimulates pancreatic volume and bicarbonate output and suggest that central secretin may play a role in the regulation of exocrine pancreatic secretion.

Epidermal growth factor enhances intestinal mitotic activity and DNA content after acute abdominal radiation.

BACKGROUND: Mediators of radiation-induced enteritis and colitis remain undefined. Epidermal growth factor (EGF) is an endogenous peptide that is trophic to the gastrointestinal tract. We tested the hypothesis that EGF enhances DNA synthesis and mitotic activity and prevents acute radiation enteritis after total abdominal radiation. METHODS: Four equal groups (n = 6) of Sprague-Dawley rats were studied: I (control), II (radiation), III (EGF), and IV (radiation + EGF). Animals in groups III and IV received EGF (10 micrograms/kg) every 8 hours for 48 hours before radiation exposure and for 72 hours after radiation, and the remaining animals were given an equal volume of vehicle. Animals in groups II and IV were administered a single dose of abdominal radiation (1000 cGy) 48 hours after the start of either vehicle or EGF. Distal ileum and colon were harvested 72 hours after radiation, examined histologically, and assayed for total DNA content. RESULTS: Group II or radiated animals had diarrhea, significant weight loss (p < 0.05), and decreased food consumption consistent with acute clinical radiation enteritis. Mitotic activity and total DNA content were significantly reduced (p < 0.05) when compared with group I (nonradiated controls). Group IV animals treated with EGF and exposed to radiation did not suffer the acute clinical manifestations of radiation enteritis. In addition, total DNA content and mitotic activity of the terminal ileum increased significantly (p < 0.05), and a significant increase in mitotic activity occurred in the distal colon when compared with radiated controls. CONCLUSIONS: The results of this study suggest that (1) a decrease in mitotic activity and total DNA content occurs early and persists for at least 72 hours after acute radiation, (2) EGF treatment significantly increases small and large bowel mitogenicity in acutely radiated animals, and (3) EGF significantly decrease the acute clinical manifestations of radiation enteritis.

Pyeloduodenal fistula: a previously undescribed complication of Stamm gastrostomy.

A variety of complications have been described after placement of a Stamm gastrostomy in infants and children, including gastric volvulus, pancreatitis, jaundice, gastroduodenal mucosal intussusception with gastric outlet obstruction, and even aortogastric fistula. However, this is the first report of pyeloduodenal fistula after Stamm gastrostomy in a 4 1/2-month-old boy. The child successfully underwent nonoperative therapy; he was treated by withdrawing the gastrostomy tube (Foley catheter) from the renal pelvis, bowel rest, and total parenteral nutrition. After the case presentation is a brief review of this rare entity, with its clinical presentation and pathophysiological differences between adult and pediatric cases. Various treatment options, both operative and nonoperative, are also described.

Stimulated pancreatic exocrine secretion does not require pancreatic hyperemia in rats. Potential cholinergic role.

Although blood flow and cholinergic tone influence gastric and salivary gland secretion, their role in pancreatic secretion is poorly defined. The purpose of the present study was: (1) to test the hypothesis that an increase in pancreatic blood flow accompanies stimulated pancreatic exocrine secretion, and (2) to examine the effects of cholinergic agents on basal and stimulated blood flow using hydrogen gas clearance. Stimulated pancreatic exocrine secretion (secretin 0.4, 0.8, 1.6 micrograms/kg/hr) resulted in a significant (P < 0.005) increase in secretory volume; however, pancreatic blood flow was not significantly changed, and a negative correlation between blood flow and secretion was observed. A pharmacologic dose of secretin (5.0 micrograms/kg/hr) resulted in a significant (P < 0.05) increase in pancreatic blood flow, which was inhibited by atropine (5.0 micrograms/kg/hr) infusion. Although 2-deoxyglucose caused a significant decrease (P < 0.03) in basal pancreatic blood flow, atropine had no effect on basal blood flow levels. These observations suggest that: (1) under physiologic conditions, secretin- or 2-deoxyglucose-stimulated pancreatic secretion does not require pancreatic hyperemia; (2) a pharmacologic dose of secretin does produce pancreatic hyperemia, perhaps through a local cholinergic mechanism; (3) peripheral cholinergic tone does not contribute significantly to basal pancreatic blood flow; and (4) basal pancreatic blood flow may be influenced by central mechanisms.

Gallbladder mucosal blood flow increases during early cholesterol gallstone formation.

Gallbladder absorption increases during early cholesterol gallstone formation and is influenced by the intraluminal presence of lithogenic bile. The effect of lithogenic bile on gallbladder mucosal blood flow is unknown. The current study tested the hypothesis that the presence of lithogenic gallbladder and hepatic bile enhances gallbladder mucosal blood flow in cholesterol-fed (0.4%) prairie dogs, as determined by hydrogen gas clearance. Gallbladder mucosal blood flow in control animals was 35.57 +/- 3.9 mL.min-1.100 g-1. In contrast, basal gallbladder mucosal blood flow in cholesterol-fed animals was significantly (P less than 0.01) increased to 64.94 +/- 8.7 mL.min-1.100 g-1. In crossover studies, the addition of lithogenic gallbladder bile to control animals (n = 6) resulted in a significant (P less than 0.025) 26% increase in gallbladder mucosal blood flow, whereas the addition of nonlithogenic gallbladder bile into gallbladders of cholesterol-fed prairie dogs resulted in a significant (P less than 0.025) 58% decrease in gallbladder mucosal blood flow. Similarly, hepatic bile crossover studies showed that the addition of lithogenic hepatic bile to control gallbladders significantly increased (P less than 0.025) gallbladder blood flow by 30%, whereas instillation of nonlithogenic hepatic bile in gallbladders of cholesterol-fed animals significantly (P less than 0.025) decreased gallbladder mucosal blood flow by 29%. These results suggest that alterations in gallbladder mucosal blood flow, influenced by the presence and absence of lithogenic bile, may play a role in cholesterol gallstone formation.

Afferent loop obstruction presenting as acute pancreatitis and pseudocyst: case reports and review of the literature.

Afferent loop obstruction after gastrectomy and Billroth II reconstruction is an uncommon problem. Complete acute obstruction requires emergent laparotomy. However, chronic obstruction may begin insidiously and its symptoms may reflect other gastrointestinal diseases. Two patients are described who developed acute abdominal pain, marked hyperamylasemia, and palpable abdominal masses 5 and 15 years after Billroth II gastrectomy. The masses were initially interpreted as pancreatic pseudocysts. Both patients were found to have chronically obstructed afferent limbs, and in one the obstruction was associated with hundreds of stasis stones within the afferent limb. Surgical decompression was accomplished in each patient. Patients who have undergone Billroth II reconstruction have signs, symptoms, and laboratory findings consistent with acute pancreatitis. A history of previous gastrectomy, recurrent or severe abdominal pain, hyperamylasemia with characteristic tomography, and endoscopic findings will establish the diagnosis and necessitate surgical evaluation and intervention.

Delayed reconstructive surgery for complex enterocutaneous fistulae.

A retrospective analysis was performed of 51 consecutive patients with complex enterocutaneous fistulae who underwent delayed reconstructive surgery. In this group of seriously ill patients, gastrointestinal continuity was restored in 94 per cent and the mortality rate was 4 per cent. The authors believe that patients with multiple or recurrent fistulae, or those associated with large abdominal wall defects can be managed through a staged multi-disciplined approach in which definitive surgery is deferred beyond the usually recommended period of six weeks.

Postoperative wound infection associated with Vibrio parahaemolyticus in a patient without exposure to seawater.

This report describes a case of wound infection associated with Vibrio parahaemolyticus. The patient had ingested steamed crabs 7 days before admission for surgical treatment of intestinal obstruction due to colon carcinoma. The Vibrio sp. was isolated from postoperative wound drainage as well as from stool. Recovery was uneventful.

Recurrent hepatic hemangiomas. Possible association with estrogen therapy.

Hemangiomas are the most common benign tumors occurring in the liver. However, the natural history of hepatic hemangiomas has not been well defined. Four patients (3 women, 1 man) with recurrent giant liver hemangiomas underwent either surgical or radiation therapy as initial treatment for the primary tumor. The average time until recurrence was 14 years, and each tumor weighed more than 600 g. Each of the female patients had been given chronic estrogen (Premarin) replacement therapy. Three of the four patients underwent surgical resection for intractable symptoms or progressive enlargement. It is believed that estrogen replacement therapy may play a role in the pathogenesis of these tumors. Furthermore, operative intervention should be considered in patients with recurrent giant liver hemangioma.

Influence of motilin and cholecystokinin on sphincter of Oddi and duodenal mobility.

The sphincter of Oddi and the duodenum exhibit cyclical activity in phase with the migrating myoelectric complex. Both motilin and cholecystokinin have been shown to modulate gastrointestinal and sphincter of Oddi motility. However, previous studies have not monitored the effects of these hormones on simultaneously recorded sphincter of Oddi and duodenum pressures. The present investigation was undertaken, therefore, to determine the influence of both motilin and cholecystokinin on simultaneously recorded sphincter of Oddi and duodenal motility. In seven anesthetized prairie dogs, a triple-lumen, side-hole, pressure-monitored perfusion catheter was positioned with the proximal port in the sphincter of Oddi and the distal port in the duodenal lumen. Sphincter of Oddi and duodenal motility was recorded before and during 20-min infusions of motilin and cholecystokinin octapeptide (CCK-8) at 1, 10, and 100 ng.kg-1.min-1. Both hormones produced dose-related increases in sphincter of Oddi and duodenal motility. No response was observed with either hormone at 1 ng.kg-1.min-1. At 10 ng.kg-1.min-1, the duodenum was slightly more sensitive to motilin than to CCK-8, while the sphincter of Oddi was equally affected by both hormones. At 100 ng.kg-1.min-1, both hormones stimulated the sphincter of Oddi and the duodenum equally. These data indicate that in the prairie dog, both motilin and cholecystokinin stimulate sphincter of Oddi and duodenal motility.

The role of dietary iron in pigment gallstone formation.

Recent studies suggest that dietary factors may be responsible for the increasing incidence of pigment gallstones. Although iron deficiency alters the activities of several hepatic enzymes, its effects on biliary lipid metabolism are not known. The aim of this study was to define the role of dietary iron in pigment gallstone formation. Three groups of prairie dogs were maintained for 2 months on either a control chow (iron-198 ppm), a high-carbohydrate diet with normal iron levels (CHO group; iron-220 ppm), or a high-carbohydrate, iron-deficient (iron-56 ppm) diet (CHO-FeD group). Serum analysis confirmed iron deficiency in the CHO-FeD group. The CHO animals had a significant (p less than 0.01) increase in hepatic bile phospholipids, while CHO-FeD animals had increased (p less than 0.01) concentrations of phospholipids and cholesterol as compared with controls. Similar findings were noted in gallbladder bile with the addition of increased calcium levels in both carbohydrate groups. Calcium bilirubinate crystals and stones were found in only 17% of CHO animals, as compared with 67% of CHO-FeD animals. These data indicate that consumption of diets rich in carbohydrates but deficient in iron alters hepatic metabolism of cholesterol and may be an important etiologic factor in pigment gallstone formation. Iron supplementation may prevent pigment gallstones in certain high-risk groups.

Altered gallbladder concentration of biliary lipids during early cholesterol gallstone formation.

Whether gallbladder absorptive function is altered during formation of cholesterol gallstones is unclear. We tested the hypothesis that alterations in biliary lipid composition present during early cholesterol gallstone formation enhance gallbladder absorption, as manifested by an increase in the ratio of gallbladder to hepatic bile lipid concentrations. Prairie dogs received either control or a 0.4% cholesterol-enriched chow for two or six weeks. The bile acid pool of each animal was labeled with [14C]cholic acid. Gallbladder and hepatic bile were analyzed for lipid composition with calculation of indices for cholesterol saturation, gallbladder stasis, and gallbladder absorption. Animals maintained on cholesterol-enriched chow for two weeks had a significant increase, as compared to controls, in the ratio of gallbladder to hepatic bile concentrations of cholesterol (8.66 +/- 1.09 vs 5.76 +/- 0.48), phospholipids (4.76 +/- 0.42 vs 3.21 +/- 0.34), bile acids (6.42 +/- 2.20 vs 3.54 +/- 0.46), and total lipid content (6.22 +/- 0.94 vs 3.64 +/- 0.43). These changes occurred at a time when gallbladder stasis is present and cholesterol crystals are forming, but prior to stone formation. Similar findings were noted in six-week cholesterol-fed prairie dogs. We propose the uniformly increased ratios of biliary lipids result from enhanced gallbladder absorption of water and sodium. The resulting increase in solute concentration may promote nucleation and, therefore, may be an important etiologic factor in cholesterol gallstone formation.

Effects of peptide YY on gallbladder motility.

The effects of peptide YY (PYY) on cholecystokinin-stimulated gallbladder contraction were investigated in the prairie dog model. Twelve animals underwent laparotomy with catheter placement into the gallbladder and common bile duct (vent). The gallbladder was continuously perfused with [14C]polyethylene glycol-labeled lactated Ringer at 0.03 ml/min, and vent effluent was collected at 2.5-min intervals. All animals received 20 min of intravenous infusion of cholecystokinin octapeptide (CCK-OP), 2.5 ng X kg-1 X min-1, immediately followed by 60-min infusions of either lactated Ringer (LR) or synthetic PYY, 10 or 50 ng X kg-1 X min-1. When LR was infused after CCK-OP, gallbladder filling increased by 15.4 +/- 10.5% with minimal changes in gallbladder pressure. Infusion of PYY10 resulted in a significant increase in gallbladder volume (P less than 0.05) and filling (P less than 0.01) with a significant decrease in intragallbladder pressure (P less than 0.05). Similar findings were noted with PYY50. These data indicate that synthetic PYY significantly augments gallbladder filling after CCK-OP-stimulated gallbladder contraction. These findings, coupled with the observation that PYY inhibits pancreatic secretion, suggest that this peptide may be the "anti-CCK" hormone and may have an important role in regulating biliary activity postprandially.

Pancreatic polypeptide enhances postcontractile gallbladder filling in the prairie dog.

The hypothesis that pancreatic polypeptide promotes postcontractile gallbladder filling was tested in the prairie dog model. Fifteen animals underwent laparotomy with catheter placement into the gallbladder, distal common bile duct (vent), and femoral vein. The gallbladder was perfused with [14C]polyethylene glycol labeled lactated Ringer's solution at 0.03 ml/min and vent effluent was collected at 2.5-min intervals. All animals received a 20-min intravenous infusion of cholecystokinin-octapeptide, 2.5 ng/kg X min, immediately followed by 60-min infusions of either lactated Ringer's solution or bovine pancreatic polypeptide (PP), 10 or 50 ng/kg X min. Gallbladder emptying and intragallbladder pressure were similar for all three groups after cholecystokinin-octapeptide. When lactated Ringer's was administered after cholecystokinin-octapeptide, gallbladder filling increased by 15.6% with a minimal change in gallbladder pressure. In contrast, infusion of PP10 resulted in a significant (p less than 0.02) increase in gallbladder filling, 64.1% +/- 17.1%, and a significant (p less than 0.05) decrease in intragallbladder pressure, as compared to controls. Similar findings were noted with PP50. These data indicate that exogenous PP significantly increases gallbladder filling after cholecystokinin-induced gallbladder contraction. This enhanced filling results from gallbladder relaxation as manifested by decreased intraluminal pressure. These findings coupled with the observation that serum PP levels remain elevated for up to 6 h after a meal suggest that PP may play a role in the regulation of postprandial gallbladder filling.

In vivo gallbladder absorption: a new dual-isotope technique.

Available methods for measuring in vivo gallbladder absorption preclude the use of animals in which hepatic bile enters the gallbladder via accessory or aberrant channels. However, accessory bile ducts are present in many of the animal models currently used in gallstone research. The aim of this study, therefore, was to evaluate a new dual-isotope technique that corrects for accessory bile flow and to compare data on electrolyte and water absorption with those derived from the standard, single-isotope technique. Prairie dogs underwent gallbladder exclusion by cystic duct ligation and common bile duct cannulation. Carbon 14-polyethylene glycol-labeled lactated Ringer's solution was instilled into the gallbladder while tritiated cholic acid was administered intravenously to label the bile acid pool. There is no correlation between water or electrolyte absorption and time, nor between water and electrolyte absorption, when these parameters are calculated by the standard, single-isotope technique. In contrast, use of the dual-isotope technique quantifies accessory bile duct flow and yields a linear increase in water and electrolyte absorption, both of which are time dependent. These data suggest that the dual-isotope technique provides a means to accurately measure in vivo gallbladder absorption in animals with or without accessory bile ducts.

Enhanced gallbladder absorption during gallstone formation: the roles of cholesterol saturated bile and gallbladder stasis.

Cholesterol saturated bile and gallbladder stasis are important factors in the pathogenesis of cholesterol gallstones. The degree to which either or both of these factors affect gallbladder transport of fluid remains obscure. The authors tested the hypothesis that both cholesterol saturated bile and gallbladder stasis, and not stasis alone, promotes gallbladder fluid absorption. Prairie dogs were maintained for 2 weeks on either a control chow, total parenteral nutrition (TPN), or a 1.2% cholesterol enriched chow. The bile acid pool was labeled with 14C-cholic acid and indexes for cholesterol saturation (CSI) and gallbladder stasis (Rsa) were determined. Fluid transport was indirectly measured by calculating the ratio of gallbladder to hepatic bile concentrations of individual and total biliary lipids. Despite evidence of stasis in prairie dogs maintained on TPN, bile was unsaturated, and gallbladder absorption was not appreciably changed. In contrast, cholesterol-fed animals had cholesterol supersaturated bile, gallbladder stasis, and altered gallbladder absorption, as manifested by a significant change in the ratio of gallbladder to hepatic bile concentrations of individual and total biliary lipids. These data suggest that both cholesterol saturated bile and gallbladder stasis, and not stasis alone, are essential in promoting the enhanced gallbladder absorption, which has previously been observed during early cholesterol gallstone formation.