Helical computed tomographic cholangiography versus endosonography for suspected bile duct stones: a prospective blinded study in non-jaundiced patients.
(25/1118)
BACKGROUND: Helical computed tomography performed after intravenous administration of a cholangiographic contrast material (HCT-cholangiography) may be useful for detecting bile duct stones in non-jaundiced patients. However, this method has never been compared with other non-invasive biliary imaging tests. AIMS: To compare prospectively HCT-cholangiography and endosonography (EUS) in a group of non-jaundiced patients with suspected bile duct stones. METHODS: Fifty two subjects underwent both HCT-cholangiography and EUS. Endoscopic retrograde cholangiography (ERCP), with or without instrumental bile duct exploration, served as a reference method, and was successful in all but two patients. RESULTS: Thirty four patients (68%) were found to have choledocholithiasis at ERCP. The sensitivity for HCT-cholangiography in stone detection was 85%, specificity 88%, and accuracy 86%. For EUS the sensitivity was 91%, specificity 100%, and accuracy 94%. The differences were not significant. No serious complications occurred with either method. CONCLUSIONS: HCT-cholangiography and EUS are safe and comparably accurate methods for detecting bile duct stones in non-jaundiced patients. (+info)
Phenotypic characterization of lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice. Pathophysiology Of biliary lipid secretion.
(26/1118)
The inbred C57L strain but not the AKR strain of mice carry Lith genes that determine cholesterol gallstone susceptibility. When C57L mice are fed a lithogenic diet containing 15% fat, 1% cholesterol, and 0.5% cholic acid, gallbladder bile displays rapid cholesterol supersaturation, mucin gel accumulation, increases in hydrophobic bile salts, and rapid phase separation of solid and liquid crystals, all of which contribute to the high cholesterol gallstone prevalence rates (D. Q-H. Wang, B. Paigen, and M. C. Carey. J. Lipid Res. 1997. 38: 1395;-1411). We have now determined the hepatic secretion rates of biliary lipids in fasting male and female C57L and AKR mice and the intercross (C57L x AKR)F(1) before and at frequent intervals during feeding the lithogenic diet for 56 days. Bile flow and biliary lipid secretion rates were measured in the first hour of an acute bile fistula and circulating bile salt pool sizes were determined by the "washout" technique after cholecystectomy. Compared with AKR mice, we found that i) C57L and F(1) mice on chow displayed significantly higher secretion rates of all biliary lipids, and larger bile salt pool sizes, as well as higher bile salt-dependent and bile salt-independent flow rates; ii) the lithogenic diet further increased biliary cholesterol and lecithin outputs, but bile salt outputs remained constant. Biliary coupling of cholesterol to lecithin increased approximately 30%, setting the biophysical conditions necessary for cholesterol phase separation in the gallbladder; and iii) no gender differences in lipid secretion rates were noted but male mice exhibited significantly more hydrophobic bile salt pools than females. We conclude that in gallstone-susceptible mice, Lith genes determine increased outputs of all biliary lipids but promote cholesterol hypersecretion disproportionately to lecithin and bile salt outputs thereby inducing lithogenic bile formation. (+info)
Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: integrated activities of hepatic lipid regulatory enzymes.
(27/1118)
There is no consensus whether hepatic lipid regulatory enzymes play primary or secondary roles in cholesterol cholelithiasis. We have used inbred mice with Lith genes that determine cholesterol gallstone susceptibility to evaluate the question. We studied activities of regulatory enzymes in cholesterol biosynthesis (HMG-CoA reductase), cholesterol esterification (acyl-CoA:cholesterol acyltransferase) and the "neutral" (cholesterol 7alpha-hydroxylase) and "acidic" (sterol 27-hydroxylase) pathways of bile salt synthesis in strains C57L/J and SWR/J as well as recombinant inbred (AKXL-29) mice, all of which have susceptible Lith alleles, and compared them to AKR/J mice with resistant Lith alleles. We determined hepatic enzyme activities of male mice before and at frequent intervals during feeding a lithogenic diet (15% dairy fat, 1% cholesterol, 0.5% cholic acid) for 12 weeks. Basal activities on chow show significant genetic variations for HMG-CoA reductase, sterol 27-hydroxylase, and acyl-CoA: cholesterol acyltranferase, but not for cholesterol 7alpha-hydroxylase. In response to the lithogenic diet, activities of the regulatory enzymes in the two bile salt synthetic pathways are coordinately down-regulated and correlate inversely with prevalence rates of cholesterol crystals and gallstones. Compared with gallstone-resistant mice, significantly higher HMG-CoA reductase activities together with lower activities of both bile salt synthetic enzymes are hallmarks of the enzymatic phenotype in mice with susceptible Lith alleles. The most parsimonious explanation for the multiple enzymatic alterations is that the primary Lith phenotype induces secondary events to increase availability of cholesterol to supply the sterol to the hepatocyte canalicular membrane for hypersecretion into bile. (+info)
Cholesterol inhibits spontaneous action potentials and calcium currents in guinea pig gallbladder smooth muscle.
(28/1118)
Elevated cholesterol decreases agonist-induced contractility and enhances stone formation in the gallbladder. The current study was conducted to determine if and how the electrical properties and ionic conductances of gallbladder smooth muscle are altered by elevated cholesterol. Cholesterol was delivered as a complex with cyclodextrin, and effects were evaluated with intracellular recordings from intact gallbladder and whole cell patch-clamp recordings from isolated cells. Cholesterol significantly attenuated the spontaneous action potentials of intact tissue. Furthermore, calcium-dependent action potentials and calcium currents were reduced in the intact tissue and in isolated cells, respectively. However, neither membrane potential hyperpolarizations induced by the ATP-sensitive potassium channel opener, pinacidil, nor voltage-activated outward potassium currents were affected by cholesterol. Hyperpolarizations elicited by calcitonin gene-related peptide were reduced by cholesterol enrichment, indicating potential changes in receptor ligand binding and/or second messenger interactions. These data indicate that excess cholesterol can contribute to gallbladder stasis by affecting calcium channel activity, whereas potassium channels remained unaffected. In addition, cholesterol enrichment may also modulate receptor ligand behavior and/or second messenger interactions. (+info)
Differing effects on gall-bladder motility of lanreotide SR and octreotide LAR for treatment of acromegaly.
(29/1118)
BACKGROUND: Octreotide treatment may be associated with gall stone development in up to 50% of patients with acromegaly. Two new sustained-release formulations of somatostatin analogue have been recently developed: lanreotide SR (Somatuline) and octreotide LAR (Sandostatin LAR). The incidence of gall-stone development in patients receiving these drugs has been shown to be less than 20%, but the duration of follow-up has been limited. OBJECTIVE: Prospectively to assess and compare the effects of the two new long-acting somatostatin agonists on gall bladder motility in patients with acromegaly. METHOD AND PATIENTS: Eleven patients with active acromegaly were studied. Three patients had asymptomatic gall stones at the start of the study. Ultrasound scans were performed before commencement of the treatment, and repeated during treatment with lanreotide SR and octreotide LAR. The presence of gall stones, fasting gall bladder volume (FV), residual volume (RV) and maximal percentage gall bladder emptying were measured. RESULTS: One patient developed asymptomatic small gall stones after treatment with octreotide LAR for 4 months. FV and RV were both significantly larger when patients received treatment with lanreotide SR or octreotide LAR compared with pretreatment values (P<0.05 for both). Maximal percentage gall bladder emptying was significantly reduced in patients receiving lanreotide SR or octreotide LAR compared with pretreatment (P<0.01), but was less impaired in patients receiving lanreotide SR than in those receiving octreotide LAR (P<0.01). CONCLUSIONS: Gall bladder motility is impaired in patients receiving either of these new long-acting preparations, and long-term follow-up will be needed to establish the true incidence of gall stones. (+info)
Preoperative versus postoperative endoscopic retrograde cholangiopancreatography in mild to moderate gallstone pancreatitis: a prospective randomized trial.
(30/1118)
OBJECTIVE: To determine whether endoscopic retrograde cholangiopancreatography (ERCP) and common bile duct (CBD) stone extraction should be performed routinely before surgery or'selectively after surgery in patients with mild to moderate gallstone pancreatitis. SUMMARY BACKGROUND DATA: The role and timing of ERCP in mild to moderate gallstone pancreatitis remains controversial. Routine preoperative ERCP identifies persisting CBD stones but carries risks of complications and may delay definitive care. Selective postoperative ERCP, performed only if a CBD stone is seen on intraoperative cholangiography (IOC), avoids unnecessary ERCP but risks unsuccessful stone extraction. METHODS: A prospective, randomized study of consecutive patients with gallstone pancreatitis was conducted. Using previously determined criteria, patients with acute cholangitis or necrotizing pancreatitis were excluded. Patients considered at high risk for persisting CBD stones (CBD size > or =8 mm on admission ultrasound, serum total bilirubin > or = 1.7 mg/dL, or serum amylase > or = 150 U/L on hospital day 4) were randomly assigned to routine preoperative ERCP followed by laparoscopic cholecystectomy, or laparoscopic cholecystectomy with selective postoperative ERCP and endoscopic sphincterotomy only if a CBD stone was present on IOC. Primary end points were costs, length of hospital stay, and the combined treatment failure rates (failure of diagnostic ERCP and IOC, complications of ERCP and endoscopic sphincterotomy, and complications of surgery). RESULTS: One hundred fifty-four consecutive patients with gallstone pancreatitis were evaluated prospectively for study eligibility. Sixty patients met the randomization criteria. Thirty patients were randomized to routine preoperative ERCP and 29 patients to selective postoperative ERCP (1 patient refused). Age, admission laboratory values, and APACHE II and Imrie scores were similar in both groups. By protocol, ERCP was performed in all patients in the preoperative ERCP group. In the postoperative ERCP group, ERCP was necessary in only 7 of 29 patients (24%). Mean hospital stay was significantly longer in the routine preoperative ERCP group (11.7 days) than in the selective postoperative ERCP group (9.0 days). Mean total cost was higher in the preoperative ERCP group ($9,426) than in the postoperative ERCP group ($7,798). The combined treatment failure rate was 10% in both groups. CONCLUSIONS: In patients with mild to moderate gallstone pancreatitis without cholangitis, selective postoperative ERCP and CBD stone extraction is associated with a shorter hospital stay, less cost, no increase in combined treatment failure rate, and significant reduction in ERCP use compared with routine preoperative ERCP. (+info)
A prospective audit against national standards of the presentation and management of acute pancreatitis in the South of England.
(31/1118)
BACKGROUND: The incidence of acute pancreatitis shows regional variations in the UK. AIMS: To document the incidence and presentation of acute pancreatitis in hospitals in Wessex, and to audit the process and outcome of management of patients against the UK guidelines. METHODS: A prospective survey was carried out of all patients with acute pancreatitis in a one year period, in eight geographically adjacent acute hospitals in the Wessex region. RESULTS: 186 patients with acute pancreatitis were identified, an incidence of 152 per million in the adult population. Aetiology was: gallstones 33%, alcohol 20%, idiopathic 32%, other 15%. There were 60 severe cases with 17 deaths. Age and APACHE-II score had significant relations to outcome, but delay to admission, serum amylase level, aetiology, and sex did not. The mortality rate (9.1%) was within the audit standard of 10%. Some management goals were not met: in mild cases, only one third of patients with gallstone pancreatitis had definitive treatment within four weeks. In severe cases, there was poor use of objective severity stratification (19%), low admission rates to a high dependency unit or intensive care unit (67%), and only 33% of patients had computed tomography. Only seven of 17 patients with severe gallstone pancreatitis had an urgent endoscopic retrograde cholangiopancreatography. CONCLUSIONS: The incidence of clinically diagnosed acute pancreatitis in England continues to rise. Current management of acute pancreatitis is suboptimal when compared with evidence based UK guidelines but the mortality rate was within the guideline standard. (+info)
Laparoscopic cholecystectomy: experience with 303 patients over the initial four years.
(32/1118)
A total of 303 patients underwent attempted laparoscopic cholecystectomy (LC) over a four-year period by two consultant surgeons or a senior trainee under their supervision. The procedure was completed in 291 with a conversion rate to open cholecystectomy of 3.9% and a median postoperative length of stay of two days, range zero to nine days. In eighteen patients the indication for LC was failure of symptoms to settle, two of whom required conversion (11.1%). Diathermy dissection was avoided in Calot's triangle and dissection started at the junction of Hartmann's pouch and cystic duct with full mobilisation of this area prior to clip application. Pre-operative endoscopic retrograde cholangiopancreatography ERCP was performed in patients suspected of having common bile duct stones without routine intra-operative cholangiography. There was one death in this series (0.3%) and an overall complication rate of 6.3 %. There was no incidence of either bile duct injury or leak. LC can be performed with a low complication rate with attention to careful dissection technique in the region of Calot's triangle. (+info)