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PubMed2001

MDR3 gene defect in adults with symptomatic intrahepatic and gallbladder cholesterol cholelithiasis.

BACKGROUND & AIMS: Many studies indicate that gallstone susceptibility has genetic components. MDR3 is the phosphatidylcholine translocator across the hepatocyte canalicular membrane. Because phospholipids are a carrier and a solvent of cholesterol in hepatic bile, we hypothesized that a defect in the MDR3 gene could be the genetic basis for peculiar forms of cholesterol gallstone disease, in particular those associated with symptoms and cholestasis without evident common bile duct stone. METHODS: We studied 6 adult patients with a peculiar form of cholelithiasis. MDR3 gene sequence was determined by reverse-transcription polymerase chain reaction amplification of mononuclear cell RNAs followed by direct sequencing. Hepatic bile was analyzed in 2 patients. RESULTS: All patients shared the following features: at least 1 episode of biliary colic, pancreatitis, or cholangitis; biochemical evidence of chronic cholestasis; recurrence of symptoms after cholecystectomy; presence of echogenic material in the intrahepatic bile ducts; and prevention of recurrence by ursodeoxycholic acid therapy. Hepatic bile composition showed a high cholesterol/phospholipid ratio and cholesterol crystals. In all patients, we found MDR3 gene mutations involving a conserved amino acid region. CONCLUSIONS: These preliminary observations suggest that MDR3 gene mutations represent a genetic factor involved in this peculiar form of cholesterol gallstone disease in adults. They require further studies to assess the prevalence of MDR3 gene defects in symptomatic and silent cholesterol gallstone disease.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2001

Cholelithiasis and hyperthyroidism in a cat.

A 14-year-old domestic short-hair cat presented with a history of intermittent malaise and increased drinking. A diagnosis of hyperthyroidism and cholelithiasis was made by a combination of blood testing, radiography and ultrasonography. After medical management of hyperthyroidism, thyroidectomy and cholecystectomy were successfully performed. Removed choleliths were comprised of calcium carbonate and bilirubinate. Histopathological analysis of tissue suggested low grade pancreatic and hepatobiliary disease, as well as hyperthyroidism, might have contributed to stone formation.

Animals↗

PubMed1978

[Ultrasound diagnosis of cholelithiasis: comparison with radiological studies (author's transl)].

Results of ultrasonic anc cholecystographic (oral or intravenous) gall-bladder studies were compared retrospectively. 302 radiological studies of the gall-bladder, 156 oral and 146 intravenous cholecystograms, had been performed on 223 patients tested by ultrasound within six months. The gall-bladder was visualised by ultrasound in 217 (97.3%), in the intravenous cholecystogram in 92 of 146 (63%) and the oral cholecystogram in 82 of 156 (53%). The diagnosis of cholelithiasis by ultrasound was made in 97 of 223 cases, confirmed in 96 by further studies or operation. There was only one false-positive result. 143 radiological studies in these 97 patients gave 87 negative cholecystograms, gall-stones being directly demonstrated radiologically in only 46. There was one false-positive intravenous cholecystogram. In a further 97 patients ultrasound studies failed to demonstrate any gall-bladder disease, but in three of them radiology demonstrated stone (2.9% false-negative results). Amond 49 normal intravenous cholecysto-cholangiograms 47 were confirmed; once the diagnosis was made by ultrasound and at surgery (2% false-negative results). Oral cholecystography was the least reliable study. In every fourth negative test ultrasound and intravenous contrast-medium injection demonstrated a normal gall-bladder (28% false-positive).

Administration, Oral↗

PubMed2002

[Molecular genetics of cholesterol cholelithiasis: identification of human and murine gallstone genes].

Cholesterol cholelithiasis is one of the most common gastroenterological diseases in Western countries. It is a polygenic disease resulting from disturbed biliary cholesterol homeostasis. Association studies identified six human gallstone candidate genes. Polymorphisms in the genes encoding the apolipoproteins B and E, phospholipid flippase ( ABCB4), cholesterol ester transfer protein ( CETP), cholesterol-7alpha-hydroxylase ( CYP7A1) and ileal bile acid transporter ( SLC10A2) are correlated with gallstone prevalence. Quantitative Trait Locus (QTL) analysis localises additional unknown gallstone genes in inbred mice. Based on the natural variation of cholesterol gallstone susceptibility among different inbred strains, 5 lithogenic ( Lith) loci have been identified. Hepatobiliary transporters (e. g. bile salt export pump Abcb11) and key proteins of the lipoprotein metabolism (e. g. hepatic lipase Lipc) could be established as creedal candidate genes for Lith loci. The rapid progress of mouse and human genome projects provides the basis for the analysis of orthologous human LITH genes in gallstone patients, which might offer new prospects for individual risk assessment and molecular targets for stone prevention.

Animals↗

PubMedDate not supplied

[Cholelithiasis in the neonatal period].

We report about a four weeks old male infant who developed jaundice with cholangitis and fever caused by cholelithiasis which could be confirmed by sonographic examination. Familiar history revealed several relatives with gallstones.

Cholangitis↗

PubMed1991

[Diagnostic value of ultrasonographic testing of the gallbladder function in cholelithiasis].

Decrease in gall-bladder volume after intake of a test meal was assessed by ultrasound in 30 patients (24 females, 6 males; mean age 55 [22-82] years) with indications for elective or early elective cholecystectomy for cholelithiasis. Patients were assigned to three groups, based on intraoperative and histological gall-bladder changes: group 1 (n = 17), without changes or with mild chronic cholecystitis; group 2 (n = 4), with severe chronic inflammatory changes; group 3 (n = 9), with acute cholecystitis or cystic duct occlusion. A volume decrease of at least 30% after the test meal excluded only acute wall inflammation (negative predictive value 95.5%), while a volume reduction of at least 50% made it possible in a high percentage of cases (negative predictive value 88.2%) to predict correctly an absence of severe chronic wall changes. Before organ-preserving treatment (extracorporeal lithotripsy or local litholysis) is undertaken, gall-bladder volume reduction of at least 50% should be documented.

Acute Disease↗

PubMed1986

Chronology of cholelithiasis. Dating gallstones from atmospheric radiocarbon produced by nuclear bomb explosions.

We investigated the natural history of cholelithiasis in 59 samples of stones from the gallbladder or common bile duct in 15 patients, using as a tracer for the timing of stone formation the 14C released into the environment during nuclear weapons testing. The ages of the stones were correlated with the dates of onset of symptoms and with other clinical data. None of 11 symptomatic patients had symptoms or complications until at least two years (mean +/- SD, 8.0 +/- 5.1 years) after stone formation began. There was a lag time of 11.7 +/- 4.6 years between initial stone formation and cholecystectomy. The growth rates of stones from 11 symptomatic patients and 4 asymptomatic patients were similar (2.6 +/- 1.4 and 2.6 +/- 1.1 mm per year). Studies of two stones retrieved from the common bile duct showed that one had the same age as a cholecystic stone; the other, removed two years after cholecystectomy, apparently grew in the common bile duct. The long latency period between the formation of gallstones and the onset of symptoms indicates that interruption of the natural progression of gallstone disease is potentially possible with medical therapy.

Carbon Radioisotopes↗

PubMed1987

A comparison of the effects of soya-bean protein and casein on bile composition, cholelithiasis and serum lipoprotein lipids in the vervet monkey (Cercopithecus aethiops).

1. Two groups of vervet monkeys (Cercopithecus aethiops) were fed on high-cholesterol diets which differed only with respect to the protein source. In one group casein was the only protein source, while the other group received only soya-bean protein. 2. Samples of blood, bile and liver biopsy material were collected at the commencement of the study and at 3-monthly intervals until termination 12 months later. 3. At the end of the experimental period all the animals (n 19) had high plasma cholesterol levels and had developed pigment gallstones, the compositions and weights of which were not related to the protein source or to plasma cholesterol levels. Gallstone weight was related to the presence of acidic and sulphated mucins in gallbladder mucosa. We were also unable to confirm the hypocholesterolaemic effect of soya-bean protein which has been demonstrated previously in rhesus monkeys and hamsters. Bile composition and plasma lipids did not differ significantly between the casein-fed and soya-bean fed animals. Lithogenic index was below 1 for both groups and did not differ significantly between the two groups. 4. No significant difference was found in the severity of cholelithiasis between the casein-fed and the soya-bean-fed animals.

Animals↗

PubMed1979

Cholelithiasis. Review of advances in research.

Cholelithiasis is now known to result from multiple causes and to have distinct clinical correlates. New knowledge about its pathophysiology and relationship to altered hepatic metabolism, the enterohepatic circulation, and gallbladder function has led to theories of prevention and to medical methods of treatment, including dissolution of stones by bile acid therapy.

Adult↗

PubMed2006

Sickle cell intrahepatic cholestasis with cholelithiasis.

Sickle cell intrahepatic cholestasis (SCIC) is a rare complication seen in sickle cell patients who present with sudden onset of RUQ pain, progressive hepatomegaly, mild elevation of transaminases, coagulopathy, and extreme hyperbilirubinemia. Early recognition of this entity is essential to avoid life-threatening complications. Diagnosis can be challenging given the overlap in clinical presentation with other conditions affecting the hepatobiliary biliary system in sickle cell anemia such as hepatitis, cholecystitis, and hepatic crisis. Treatment is currently limited to exchange transfusion. The authors present two patients with SCIC and cholelithiasis; the clinical picture of one is complicated by choledocholithiasis.

Adolescent↗

PubMed2002

Indinavir-induced cholelithiasis in a patient infected with human immunodeficiency virus.

We report the first case of acute cholecystitis due to indinavir-induced cholelithiasis in a patient infected with human immunodeficiency virus who had been receiving indinavir for 56 months. Infrared spectroscopy demonstrated that the gallstone was composed of indinavir monohydrate (50%), calcium bilirubinate (28%), calcium palmitate (10%), cholesterol (7%), and proteins (5%). The role of high-level chronic unconjugated hyperbilirubinemia coupled with high blood concentrations of indinavir is discussed.

Acute Disease↗

PubMed1993

Techniques for the simultaneous management of incarcerated ventral herniae and cholelithiasis via laparoscopy.

Two patients presented with symptomatic cholelithiasis and cholecystitis and ventral herniae. In Case 1, an incarcerated supraumbilical hernia was present in a morbidity obese patient. In Case 2, an incarcerated incisional hernia was present. Both patients underwent laparoscopic cholecystectomy and simultaneous herniorrhaphy. Technical details of the operative technique are presented.

Adult↗

PubMed1985

The association between cholesterol cholelithiasis and coronary heart disease in Framingham, Massachusetts.

A relationship between cholesterol gallstone disease and atherosclerosis or its sequellae has long been postulated but has never been adequately proven. Data for this investigation of the relationship of diagnosed cholesterol cholelithiasis to subsequent incident coronary heart disease were obtained from a review of the pre-existing prospectively collected medical records of the 5,209 individuals followed since 1952 as members of the original cohort of the Framingham Heart Study. Preliminary univariate examination of these data, making no correction for time ordering of the conditions or for shared risk factors, indicated a significant modest positive association in men but no relationship in women. Logistic multiple regression analyses, allowing for the effects of time ordering and for eight standard coronary disease risk factors, confirmed these findings. The authors speculate that the presence of cholesterol gallstones in male patients may be indicative of an unfavorable lipoprotein profile. These results have clinical implications in that male gallstone patients are at increased risk for subsequent coronary disease and should be monitored accordingly. This investigation marks the first time that a relationship between these conditions has been established using a longitudinal cohort study approach.

Adult↗

PubMed1976

Abnormalities in gallbladder morphology and function in patients with cholelithiasis.

Thirty-seven symptomatic cholelithiasis patients who had cholecystectomy were studied to determine the relationships between clinical manifestations, histologic findings and gallbladder absorptive capability. A clinical score was calculated from clinical data which we thought might be predictive of abnormal gallbladder histology. Histologic parameters indicative of gallbladder disease were used to calculate a histologic score. Shortcircuit current measurements, which reflect gallbladder sodium absorption,were used to assess absorptive function. Patients with very high clinical scores, indicative of pronounced clinical score was not predictive of histologic findings or absorptive function of the gallbladder is directly related to the degree of histologic abnormality, and that absorptive capability is not an all-or-none phenomenon. The data also show that visualization on oral cholecystography is an unreliable measure of gallbladder absorptive capability.

Cholecystography↗

PubMed1981

The role of Chiba-needle cholangiography in the diagnosis of possible acute pancreatitis with cholelithiasis.

In patients with suspected severe acute pancreatitis and known or suspected cholelithiasis, it may be extremely difficult to exclude the diagnosis of gangrenous cholecystitis or obstructive cholangitis by nonoperative means. Since early intra-abdominal surgery has, in our experience, led to markedly increased morbidity in patients with gallstone pancreatitis, non-operative visualization of the biliary tree by percutaneous transhepatic Chiba-needle cholangiography (PTCNC) has been evaluated in 14 patients with suspected acute pancreatitis in whom life-threatening acute biliary disease could not be excluded by other nonoperative means. The final diagnosis was acute pancreatitis in nine patients (Group A) (mean serum amylase 3242 SU%) and acute biliary disease with hyperamylasemia in five patients (Group B) (mean serum amylase 2084 SU%). PTCNC made visualization of the biliary system possible in all patients and excluded the diagnosis of cystic duct or common duct obstruction in each case. Following PTCNC, potentially hazardous early laparotomy was avoided in eight of nine Group A patients. Biliary surgery was undertaken on day 3 to 13 in four Group B patients. When early laparotomy may be needed to evaluate or treat possible life-threatening acute biliary disease but is considered undesirable because of possible acute pancreatitis. PTCNC appears to be a safe and effective nonoperative method of obtaining precise anatomical delineation of the biliary tree.

Acute Disease↗

PubMed1983

Management of cholelithiasis in patients with abdominal aortic aneurysm.

Gallstones were detected in 42 of 865 patients with abdominal aortic aneurysm (4.9%). Eighteen patients underwent concomitant aneurysm resection and cholecystectomy. Eleven patients had aneurysmectomy without cholecystectomy. Thirteen patients underwent cholecystectomy alone. There were no significant increases in operative mortality, duration of operation, or length of hospital stay when cholecystectomy was added to aneurysm resection. However, there was one instance of prosthetic infection which occurred in a patient who did not have his graft retroperitonealized prior to cholecystectomy, and who also underwent gastrostomy and drainage of the liver bed. There have been no graft complications in the remaining 17 consecutive patients who had their graft retroperitonealized prior to cholecystectomy. Nine of 11 patients who underwent aneurysmectomy without cholecystectomy experienced an episode of acute cholecystitis during a mean follow-up period of 2.9 years. Two of these episodes occurred in the immediate postoperative period and one patient died of biliary sepsis. On the basis of these findings, concomitant aneurysmectomy and cholecystectomy is advised in those patients with cholelithiasis undergoing aortic aneurysm resection providing no contraindications exist.

Aged↗

PubMed1983

Cholelithiasis in children with immunoglobulin A deficiency: a new gastroenterologic syndrome.

In view of the role of immunoglobulin A (IgA) in the local host defenses of the gut and biliary tract, and the association of IgA deficiency with various intestinal disorders, an ultrasonographic study was performed to determine the prevalence of gallstones in selective IgA deficiency. Eight of 13 children (three girls and five boys) with selective IgA deficiency had abnormal biliary sonograms. Four had cholelithiasis, and four had biliary sludge only. IgA deficiency may predispose to gallbladder infection, and thus to the development of gallstones. Decreased bile acid pool due to intestinal losses, and biliary stasis due to reduced hormonal gallbladder stimulation may also play a role in some cases, but further studies are needed. This association adds a new gastrointestinal abnormality to those known to be associated with selective IgA deficiency.

Adolescent↗

PubMed1983

Cholelithiasis in adult cystic fibrosis.

The clinical picture of adult cystic fibrosis is usually dominated by respiratory failure. Hepatic dysfunction occurs commonly, but symptomatic cholelithiasis is a rarely reported complication of the disease. This case of common duct obstruction emphasizes the broad spectrum of sequelae that may be expected in this newly emerging population of adults with cystic fibrosis.

Adult↗