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PubMed1993

Cholesterol cholelithiasis in the prairie dog: role of mucin and nonmucin glycoproteins.

The aims of this study were to examine the effect of exogenous prostaglandin on mucin secretion and to determine the role of nonmucin glycoproteins on gallstone formation in the prairie dog model of cholesterol cholelithiasis. The concentration of total glycoprotein and nonmucin glycoproteins was measured in gallbladder bile from four groups of prairie dogs fed a control diet or a diet supplemented with 1.2% cholesterol with or without simultaneous subcutaneous administration of prostaglandin E1. Cholesterol feeding resulted in an increased concentration of concanavalin-A binding-proteins in gallbladder bile associated with an increase in pronucleating activity in vitro. Treatment with prostaglandin E1 and cholesterol feeding was associated with a significant increase in the incidence of cholesterol gallstone formation. Prostaglandin E1 treatment in the cholesterol-fed animals increased biliary concentrations of total glycoprotein and concanavalin-A-binding glycoproteins. Therefore the increased biliary glycoprotein level in cholesterol-fed, prostaglandin E1-treated prairie dogs, which reflects higher levels of mucin and nonmucin glycoproteins, appears to be an important factor in gallstone formation.

Alprostadil↗

PubMed1994

Biliary phospholipases in the prairie dog model for cholesterol cholelithiasis.

Lysolecithin has been implicated as a contributing factor in the pathogenesis of cholecystitis and cholesterol cholelithiasis. The phospholipases are key enzymes in the generation of a number of metabolites including lysolecithin, but conflicting reports exist concerning the presence of these enzymes in the biliary tract. In this study, measurement of phosphatidylcholine-specific phospholipase activity by means of the hydrolysis of radiolabeled phosphatidylcholine (100 nmol) by 90 micrograms of homogenate protein during a 60-min incubation demonstrated substantial enzyme activities in gastric fundus and distal ileum (90% and 70% hydrolysis, respectively), whereas activity was virtually undetectable in gallbladder mucosa (0.7% hydrolysis). Additional studies were conducted in prairie dogs fed diets high in cholesterol or with trace amounts of cholesterol using homogenates of gallbladder mucosa, seromuscularis and full-thickness tissue, as well as samples of hepatic and gallbladder bile. The only hydrolytic activity in excess of blank values that was detected was a highly variable phospholipase A2 activity in several gallbladder biles from animals given diets with both low levels and high levels of cholesterol, with the enzyme activities of the two dietary groups being similar. These results demonstrate that prairie dog gallbladder contains extremely low levels of phospholipase activity, in marked contrast to other gastrointestinal tissues. However, there was evidence of a phospholipase A2 activity in gallbladder bile. In light of the low activity in gallbladder tissue, the source of this enzyme appears to be the liver and not the gallbladder.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2004

Spontaneous cholecysto- and hepatolithiasis in Mdr2-/- mice: a model for low phospholipid-associated cholelithiasis.

Previously, we identified needle-like and filamentous, putatively "anhydrous" cholesterol crystallization in vitro at very low phospholipid concentrations in model and native biles. Our aim now was to address whether spontaneous gallstone formation occurs in Mdr2 (Abcb4) knockout mice that are characterized by phospholipid-deficient bile. Biliary phenotypes and cholesterol crystallization sequences in fresh gallbladder biles and non-fixed liver sections were determined by direct and polarizing light microscopy. The physical chemical nature and composition of crystals and stones were determined by sucrose density centrifugation and before mass and infrared spectroscopy. Gallbladder biles of Mdr2(-/-) mice precipitate needle-like cholesterol crystals at 12 weeks of age on chow. After 15 weeks, more than 50% of Mdr2(-/-) mice develop gallbladder stones, with female mice displaying a markedly higher gallstone-susceptibility. Although gallbladder biles of Mdr2(-/-) mice contain only traces (</= 1.1 mM) of phospholipid and cholesterol, they become supersaturated with cholesterol and plot in the left 2-phase zone of the ternary phase diagram, consistent with "anhydrous" cholesterol crystallization. Furthermore, more than 40% of adult female Mdr2(-/-) mice show intra- and extrahepatic bile duct stones. In conclusion, spontaneous gallstone formation is a new consistent feature of the Mdr2(-/-) phenotype. The Mdr2(-/-) mouse is therefore a model for low phospholipid-associated cholelithiasis recently described in humans with a dysfunctional mutation in the orthologous ABCB4 gene. The mouse model supports the concept that this gene is a monogenic risk factor for cholesterol gallstones and a target for novel therapeutic strategies.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed1978

Cholelithiasis and acoustic shadowing.

The importance of the acoustic shadow in the ultrasound diagnosis of cholelithiasis has been stressed in recent reports. In vitro studies of gallstones indicate that the presence and magnitude of the acoustic shadow depend on a number of factors and suggest that a group of small stones may be demonstrable even though no acoustic shadow can be seen.

Cholecystography↗

PubMed1983

Extrahepatic bile ducts in healthy subjects, in patients with cholelithiasis, and in postcholecystectomy patients: a prospective ultrasonic study.

To determine the average diameter and the upper normal limit of the common bile duct in healthy man, 830 blood donors were examined by ultrasound. The mean diameter was 2.5 +/- 1.1 mm (SD) at the porta hepatis and 2.8 +/- 1.2 mm (SD) at the widest point, the regression coefficient between both diameters being r = 0.84. None of the healthy subjects had a diameter larger than 7 mm at any site, and in 95% of all subjects the diameters were less than 4 mm at both sites of measurement. The diameters were significantly correlated with age (r = 0.16) and weight (r = 0.11), but not with sex, height, and body surface area. In 73 patients with cholelithiasis and in 55 patients after cholecystectomy, all of whom lacked clinical or laboratory signs of biliary obstruction, the average diameters at the porta hepatis were 3.8 +/- 2.0 mm and 5.2 +/- 2.3 mm, and at the widest point 4.8 +/- 2.2 mm and 6.2 +/- 2.5 mm, respectively. It is concluded that a common bile duct with any sonographic diameter larger than 4 mm should be followed closely and evaluated further with clinical examinations such as intravenous cholangiography unless cholecystectomy has been performed.

Adolescent↗

PubMed1980

Further observations in lincomycin-induced cholelithiasis in guinea-pigs.

Further experiments are reported on Lincomycin-induced cholelithiasis in guinea-pigs. The biochemical events in the bile and blood, and the chemical composition of gallstones, have been studied. The gallstones resemble human pigment stones in chemical composition. The clear hepatic bile and the normality of the bile salt--phospholipid--cholesterol equilibrium, the rise in beta-glucuronidase and hexosamine levels with the gallbladder, have reaffirmed that epithelial injury is most probably the primary lithogenic factor. Ligation of the cystic duct and the construction of a common hepatic duct-duodenum bypass did not prevent the development of acute cholecystitis, suggesting the lithogenic factor was mediated through the blood circulation and not through the enterohepatic circulation of bile.

Animals↗

PubMed1981

Hypersecretion of mucus glycoprotein by the gallbladder epithelium in experimental cholelithiasis.

In three models of cholelithiasis (dihydrocholesterol-fed rabbits, cholesterol-cholic acid-fed mice, and Lincomycin-treated guinea pigs), the quantity and chemical composition of gallbladder epithelial mucin have been studied using (1) a spectrum of histochemical glycoprotein stains, and (2) biochemical extraction, purification and analysis of the carbohydrate components of epithelial mucin. Despite the diverse mechanism of stone induction and difference in stone composition, a common pattern of response by the epithelial mucin was observed in all three models. There was a quantitative increase in epithelial mucus production at a time before stones were formed and this increase persisted till stones were formed. There was no difference, qualitatively, between mucus produced by normal and stone-forming gallbladders.

Animals↗

PubMedDate not supplied

Cholelithiasis in patients with Gaucher disease.

Gaucher disease, the inherited deficiency of the lysosomal enzyme glucocerebrosidase, manifests with a continually expanding range of clinical features. Noting that a number of adult patients with type 1 Gaucher disease also had gallstones, we reviewed the clinical records of 66 adult patients evaluated at the National Institutes of Health with type 1 Gaucher disease. Twenty-one patients were identified who had either gallstones or a history of cholecystectomy. Of the 21 patients, 6 were male. The age at which stones were noted ranged from 19 to 70 years (mean 39 years). Thirteen of the patients had a cholecystectomy performed. Several different factors may contribute to the development of gallstones in these patients, including anemia, prior splenectomy, and hepatic involvement. Eleven of the patients were found to have chronic anemia. Fifteen of the patients underwent splenectomy. An increased biliary excretion of glucosylceramide could also contribute to cholelithiasis. To determine whether our findings were specific to our referral population, the medical records of a second series of 80 adult patients of Ashkenazi Jewish ancestry with type 1 Gaucher disease followed in Northern Israel were reviewed. Sixteen of these patients (5 male, 11 female) were also noted to have gallstones. Thus, the frequency of gallbladder involvement in patients with Gaucher disease appears to be greater than previously appreciated.

Adult↗

PubMed1993

Tobacco, ethanol, coffee, pancreatitis, diabetes mellitus, and cholelithiasis as risk factors for pancreatic carcinoma.

A hospital-based case-control study of pancreatic cancer was conducted in Athens in 1991-92. One hundred and eighty-one patients operated on for cancer of the exocrine pancreas in eight teaching hospitals formed the case series, whereas hospital patient controls and hospital visitor controls formed two independent comparison series. Cases and controls were matched by hospital, gender, and age in a 1:1:1 ratio, and every matched triplet was interviewed in person by the same researcher. Results indicate that tobacco smoking increased the risk of pancreatic cancer, whereas neither coffee drinking nor consumption of alcoholic beverages were associated with the disease. Diabetes mellitus, cholelithiasis, and pancreatitis were associated positively with risk of pancreatic cancer, whereas allergic asthma was inversely (but not significantly) related to the disease. There was a suggestion that earlier age at menarche was associated with increased risk of pancreatic cancer and that parous women were at lower risk. No consistent associations were noted with respect to gastrectomy, other medical conditions or operations, birth order, height, weight, broad occupational groups, or other reproductive variables. The two comparison series were remarkably similar with respect to the whole spectrum of the study variables.

Adult↗

PubMed1989

Inter and intra-observer variation in ultrasonographic detection of gallstones: the Multicenter Italian study on epidemiology of cholelithiasis (M.I.COL.).

Inter and intra-observer agreement in classifying the presence of gallstones by ultrasonographic images according to established criteria was studied. A film recording of 50 routine ultrasonographic examinations of the gallbladder was read by each of the 46 observers who participated in the Multicenter Italian Study on Epidemiology of Cholelithiasis (M.I.COL.). The overall Kappa score for inter-observer agreement was 0.649, while intra-observer agreement was "good" or "excellent" (Kappa scores greater than 0.60) in 75% of the observers. No statistical difference for inter-observer agreement between "novices" and "expert" echographers was found in the overall Kappa statistic or in category-specific Kappa scores (gallstone, no gallstone, doubtful and inconclusive examinations) The present study suggests that the development of explicit criteria by a group of trained echographers does not eliminate inter- and intra-observer disagreement in categorizing subjects for gallbladder stones.

Cholelithiasis↗

PubMed1996

The impact of laparoscopic cholecystectomy on the treatment of symptomatic cholelithiasis.

BACKGROUND: There has been a debate about the cost-effectiveness of laparoscopic cholecystectomy (LC), as well as a concern regarding its possible overutilization and changes in the indication for surgery. METHODS: A retrospective analysis of all cholecystectomies performed at UCDMC from 1988 to 1994 was done. The annual rate of cholecystectomy increased by 50% in 1990 when LC was introduced but has since stabilized at a rate 11% higher than the rate before LC. The disease status and severity did not change. RESULTS: The incidence of nonelective surgery remained stable at 31.2% to 37.5%. Elective cholecystectomy had lower mortality (0.16% vs 1.8%, P = 0. 029), morbidity (2.6% vs 11.2%, P = 0.0001), and conversion rate (2. 6% vs 16%, P = 0.0001) and a shorter length of stay (2.1 days vs 5.4 days), compared with nonelective procedure. CONCLUSIONS: The indication for surgery in cholelithiasis has not changed since the introduction of LC. In patients with symptomatic gallstones, early elective surgery is recommended and may be more cost-effective.

Adult↗

PubMedDate not supplied

Nephrocalcinosis, cholelithiasis, and umbilical vein calcification in a premature infant.

A case of calcification of the umbilical vein in a premature infant with nephrocalcinosis and cholelithiasis is described. Such an association might have resulted from prematurity, bronchopulmonary dysplasia, umbilical vein catheterization, total parenteral nutrition, and furosemide therapy. Follow-up ultrasound examination at 9 months of age revealed spontaneous resolution of calcification of both the gallbladder and the umbilical vein but not of the kidneys.

Calcinosis↗

PubMed1993

Bacteriological investigation of bile in patients with cholelithiasis.

The microflora in bile from the gallbladder and common bile duct was investigated in 303 patients who underwent surgery for cholelithiasis. The purpose of this study was to identify current bacteria and bacterial casts in the biliary tract and also to analyze the relationship between bactericholia at the time of operation and postoperative infection. Bile cultures were positive in 38% of all patients, although a higher incidence of positive bile cultures occurred in patients over 70 years of age (77%), those with common duct stones (83%), those with pigment stones (65%), and those who underwent gastrectomy (71%). The predominant organisms were Escherichia coli (22%), Klebsiella (18%), and Enterococcus (15%). Obligate anaerobes were less frequently seen (4%), being found only in patients with pigment stones and always mixed with aerobes. Four patients developed postoperative infections (1.3%) which were all caused by biliary bacteria. The following two factors may contribute to this low incidence of postoperative infections: our policy of operating electively whenever possible, and the prophylactic use of antibiotics to which the organisms cultured from bile are sensitive.

Adult↗

PubMedDate not supplied

Laparoscopic cholecystectomy combined with endoscopic sphincterotomy and stone extraction or laparoscopic choledochoscopy and electrohydraulic lithotripsy for management of cholelithiasis with choledocholithiasis.

Six hundred twenty-two laparoscopic cholecystectomies were performed at St. Vincent Hospital over a 14-month period. We reviewed the records of 366 of these patients who were referred to the authors. Thirty-six patients had suspected choledocholithiasis. The primary author (M.E.A.) performed 38 endoscopic retrograde cholangiopancreatography (ERCPs) on these patients for diagnosis and management. Seventeen of the 36 patients had common bile duct stones; 19 patients had negative studies. Of the 17 patients with choledocholithiasis, 15 had successful cannulation of the common bile duct, and, of these, 10 underwent laparoscopic cholecystectomy plus endoscopic sphincterotomy and extraction of the common duct stone(s). In one high-risk elderly patient, we extracted the stone from the common duct and left the gallbladder in situ. Two patients failed endoscopic cannulation and underwent open cholecystectomy with common bile duct exploration. Four additional patients, cannulated successfully, had unsuccessful endoscopic stone removal because the stones were too large or were impacted. Two of these patients underwent open cholecystectomy and common duct exploration. The two other patients underwent laparoscopic cholecystectomy and choledochoscopy through the cystic duct with the flexible choledochoscope. An electrohydraulic lithotripsy probe was then inserted through the choledochoscope to fragment the stones, and stone fragments were allowed to pass through the previously created sphincterotomy. We believe our data, supported by data in the literature, show that these alternative methods for treating choledocholithiasis are safe and effective and should be considered primary modalities for treating this condition now that laparoscopic cholecystectomy is the treatment of choice for cholelithiasis.

Cholangiopancreatography, Endoscopic Retrograde↗

PubMed1981

The changing aspects of cholelithiasis in children through a sonographic study.

Ultrasonography has made the study of the biliary tract easier. This may account for an apparent increase in the incidence of cholelithiasis in children. Twenty-nine cases of biliary stones, mostly gallstones, were seen in a 3 year period. More than half of the cases were secondary to a definite cause, among which the interruption of the enterohepatic circulation of bile salts should be emphasized. The etiological factors of biliary stones and biliary sludge appeared identical in our material.

Adolescent↗

PubMed1982

Neonatal cholelithiasis.

Cholelithiasis is very rare in the newborn infant and is usually not recognized until surgery or autopsy following perforation of the biliary tree. Two premature infants had calcified gallstones on abdominal radiographs. In one patient portal vein thrombosis was also present. The other had been treated with total parenteral nutrition (TPN) and furosemide which have recently been implicated in the development of gallstones in premature infants.

Cholelithiasis↗

PubMed1977

The usefulness of stool screening for diagnosing cholelithiasis in acute pancreatitis. A description of the technique.

Screening stools for gallstones in patients with acute pancreatitis has been found to be a valuable diagnostic procedure in clinical practice. It is particularly helpful to know that a patient with pancreatitis has gallstones and, therefore, the disease is probably caused by the passage of these stones. A detailed description of the technique employed for stool screening is presented. The procedure was applied in 51 patients recovering from an attack of gallstone pancreatitis,in 51 control patients with known gallstones disease but without acute pancreatitis, and also in 10 patients with acute alcoholic pancreatitis Gallstones were found in the feces in 47 of the 51 patients with gallstone pancreatitis (92.1%), in only 6 of the 51 control cases (11.8%) (chi square = 62.84; P less than 0.0001), and in none of the 10 patients with alcoholic pancreatitis. In the group with gallstone pancreatitis, the finding occurred within 10 days after the attack. Oral cholecystography was also accomplished an average of 12.7 days after the attack in 38 of the 61 pancreatitis patients (28 with biliary and 10 with alcoholic pancreatitis). In 27 of the 28 patients with gallstone pancreatitis (96.4%) and in 4 of the 10 patients with alcoholic pancreatitis, radiologic evidence of cholelithiasis was found. There were 19 patients with gallstone pancreatitis who did not have a cholecystogram accomplished because of jaundice, recurrent pancreatitis, previous cholecystectomy, and pregnancy. These results suggest that screening stools is as accurate and reliable as cholecystography for the diagnosis of gallstones in individuals with pancreatitis. In addition, this method has three definite advantages over cholecystography: There are no contraindications; it requires no special equipment or personnel; and it can be used much earlier than cholecystography in patients recovering from an attack of acute pancreatitis. Screening stools for gallstones should be considered an elective diagnostic procedure for current clinical application.

Acute Disease↗

PubMed1993

Relationship between cystic duct diameter and the presence of cholelithiasis.

We sought to measure cystic duct diameter in patients without biliary calculi and in those with cholelithiasis or choledocholithiasis. Using endoscopic retrograde cholangiopancreatography (ERCP), we visualized the cystic duct in 168 patients referred to our unit. These patients were distributed into three groups based on findings at ERCP: Group I (N = 57), no calculi in the gallbladder or common bile duct; group II (N = 27), stones found in the gallbladder but absent from the common bile duct; and group III (N = 34), stones present in the common bile duct with or without gallbladder stones. The diameter of the cystic duct was measured at its widest and narrowest dimensions. The largest diameter measured was greater in group III (7.72 +/- 2.29 mm) than in groups I (2.63 +/- 0.67 mm) and II (4.59 +/- 1.13 mm) (P < 0.001). The same differences were found in measurement of the smallest diameter (5.00 +/- 0.99 mm, 3.10 +/- 0.62 mm, and 1.83 +/- 0.53 mm, for groups III, II, and I, respectively) (P < 0.001). Maximal and minimal cystic duct diameter show a progressive increase at each level of disease. This increase in cystic duct size may facilitate the migration of gallstone fragments after lithotripsy and facilitate the instrumentation of the cystic duct during ERCP and laparoscopic cholecystectomy.

Adult↗