Lith6: a new QTL for cholesterol gallstones from an intercross of CAST/Ei and DBA/2J inbred mouse strains.
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A complex genetic basis determines the individual predisposition to develop cholesterol gallstones in response to environmental factors. We employed quantitative trait locus/loci (QTL) analyses of an intercross between inbred strains CAST/Ei (susceptible) and DBA/2J (resistant) to determine the subset of gallstone susceptibility (Lith) genes these strains possess. Parental and first filial generation mice of both genders and male intercross offspring were evaluated for gallstone formation after feeding a lithogenic diet. Linkage analysis was performed using a form of multiple interval mapping. One significant QTL colocalized with Lith1 [chromosome (chr) 2, 50 cM], a locus identified previously. Significantly, new QTL were detected and named Lith10 (chr 6, 4 cM), Lith6 (chr 6, 54 cM), and Lith11 (chr 8, 58 cM). Statistical and genetic analyses suggest that Lith6 comprises two QTL in close proximity. Our molecular and genetic data support the candidacy of peroxisome proliferator-activated receptor gamma (Pparg) and Slc21a1, encoding Pparg, and the basolateral bile acid transporter SLC21A1 (Slc21a1/Oatp1), respectively, as genes underlying Lith6. (+info)
Spontaneous passage of bile duct stones: frequency of occurrence and relation to clinical presentation.
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BACKGROUND: Little is known about the spontaneous passage of bile duct stones. The aim of this study was to determine the rate of spontaneous stone passage and relate it to the clinical presentation of the bile duct stone. PATIENTS AND METHODS: Prospectively collected data were studied on a total of 1000 consecutive patients undergoing laparoscopic cholecystectomy with or without laparoscopic common duct exploration. Comparisons were made between 142 patients with common bile duct stones (CBDS), 468 patients who had no previous or current evidence of duct stones, and 390 patients who had good evidence of previous duct stones but none at the time of cholecystectomy. The evidence used for previous duct stones included a good history of jaundice or pancreatitis. In patients with biliary colic or cholecystitis, abnormal pre-operative liver function tests and/or a dilated common bile duct were taken as evidence of bile duct stones. RESULTS: Of the 1000 patients studied, 532 had evidence of stones in the common bile duct at some time prior to cholecystectomy. At the time of operation, only 142 patients had bile duct stones. By implication, 80%, 84%, 93% and 55% of patients presenting with pancreatitis, colic, cholecystitis and jaundice (73% overall) had passed their bile duct stones spontaneously. All 4 patients with cholangitis had duct stones at the time of operation. CONCLUSIONS: It is likely that most bile duct stones (3 in 4) pass spontaneously, especially after pancreatitis, biliary colic and cholecystitis but less commonly after jaundice. Cholangitis appears to be always associated with the presence of duct stones at the time of operation. (+info)
Long-term prognosis after treatment of patients with choledocholithiasis.
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OBJECTIVE: This study was conducted to examine the long-term prognosis of after treatment of patients with choledocholithiasis, including the recurrence of lithiasis, and to thereby determine the best treatment modality for choledocholithiasis based on its pathological entity. SUMMARY BACKGROUND DATA: Choledocholithiasis can be caused by either primary bile duct stones that originate in the bile duct or by secondary bile duct stones that have fallen out of the gallbladder. The recurrence rates vary depending on the type of choledocholithiasis. METHODS: Two-hundred thirteen outpatients who were treated for choledocholithiasis from 1982 to 1996 were selected as subjects and monitored for a period ranging from 5 to 19 years (mean, 9.6 years). The 213 patients were divided into 3 groups: 87 patients who had undergone choledocholithotomy and T-tube drainage (including the use of the laparoscopic method), 44 patients who had undergone choledochoduodenostomy, and 82 patients whose stones were removed by endoscopic sphincterotomy (EST). Recurrence of lithiasis was examined for each type of treatment modality. RESULTS: Choledochoduodenostomy was performed in 44 cases for the purpose of preventing any recurrence. The recurrent rate was analyzed in 169 cases. Choledocholithiasis recurred in 17 of the 169 cases (10.1%). The remaining 152 patients that showed no recurrence of lithiasis were examined and compared. The diameter of the common bile duct measured during the initial treatment was more dilated in patients with recurrent lithiasis (16.6 +/- 5.9 mm) than in patients without any recurrence (9.8 +/- 4.9 mm; P < 0.05). Peripapillary diverticula were observed in 10 of the 17 patients with recurrent lithiasis (58.8%), and in 34 of the 152 nonrecurrent patients (22.3%), showing that diverticula were more common in recurrent cases (P < 0.05). Furthermore, while primary bile duct stones were found in 11 of the 17 cases with recurrent lithiasis (64.7%), primary stones were found in only 37 of the 152 nonrecurrent patients (24.3%), showing primary bile duct stones were also more common in recurrent patients (P < 0.05). The recurrent patients were examined by surgical procedure. Nine patients with choledocholithotomy and T-tube drainage had a recurrence (10.3%), and 8 patients in the EST group had a recurrence (9.8%). The recurrence rates for these procedures were higher than for cases with choledochoduodenostomy (recurrence rate: 0%, P < 0.05). In particular, lithiasis recurred in 5 of the 12 patients with T-tube drainage for primary bile duct stones (41.7%). CONCLUSION: Although choledocholithotomy and T-tube drainage, including open and laparoscopic surgery, is presently a common procedure for choledocholithiasis, this procedure will not necessarily prevent a recurrence of the disease. For older patients with primary bile duct stones, choledochoduodenostomy or EST is recommended. (+info)
Phosphatidylcholine-enriched diet prevents gallstone formation in mice susceptible to cholelithiasis.
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Cholesterol gallstones affect approximately 10-15% of the adult population in North America. Phosphatidylcholine (PC) is considered to be the main cholesterol solubilizer in bile. This study examined the effect of a PC-enriched diet on gallstone incidence in mice susceptible to cholelithiasis. The result obtained showed that the feeding of a lithogenic (LG) diet for 4 weeks or 8 weeks resulted in cholesterol gallstone incidences of 47% and 89%, respectively. These gallstone incidences were either reduced or prevented when the LG diet was enriched with 2% or 6% PC, respectively. The cholesterol saturation index (CSI) was reduced only in mice fed with LG + 6% PC diet as compared with mice fed the LG diet alone. However, in all groups, the CSI was significantly higher than in mice fed Purina chow diet. The biliary anionic polypeptide fraction (APF) was significantly increased in mice fed the LG + 2% PC diet and was reduced in those fed with LG + 6% PC diet. In conclusion, prevention or delay of gallstone formation was not due to a consistent effect on biliary lipid composition, suggesting a direct effect of PC on cholesterol solubilization and/or the effect of an additional nonlipid biliary component such as APF. (+info)
High level of deoxycholic acid in human bile does not promote cholesterol gallstone formation.
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AIM: To study whether patients with excess deoxycholic acid (DCA) differ from those with normal percentage of DCA with respect to biliary lipid composition and cholesterol saturation of gallbladder bile. METHODS: Bile was collected during operation through puncturing into the gallbladder from 122 cholesterol gallstone patients and 46 gallstone-free subjects undergoing cholecystectomy. Clinical data, biliary lipids, bile acid composition, presence of crystals and nucleation time were analyzed. RESULTS: A subgroup of gallstone patients displayed a higher proportion of DCA in bile than gallstone free subjects. By choosing a cut-off level of the 90th percentile, a group of 13 gallstone patients with high DCA levels (mean 50 percent of total bile acids) and a large group of 109 patients with normal DCA levels (mean 21 percent of total bile acids) were obtained. The mean age of the patients with high DCA levels was higher than that of the group with normal levels (mean age: 62 years vs 45 years) and so was the mean BMI (28.3 vs. 24.7). Plasma levels of cholesterol and triglycerides were slightly higher in the DCA excess groups compared with those in the normal DCA group. There was no difference in biliary lipid composition, cholesterol saturation, nucleation time or occurrence of cholesterol crystals in bile between patients with high and normal levels of DCA. CONCLUSION: Gallstone patients with excess DCA were of older age and had higher BMI than patients with normal DCA. The two groups of patients did not differ with respect to biliary lipid composition, cholesterol saturation, nucleation time or occurrence of cholesterol crystals. It is concluded that DCA in bile does not seem to contribute to gallstone formation in cholesterol gallstone patients. (+info)
Outcome of gallbladder preservation in surgical management of primary bile duct stones.
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AIM: To evaluate the methods and outcome of gallbladder preservation in surgical treatment of primary bile duct stones. METHODS: Thirty-five patients with primary bile duct stones and intact gallbladders received stone extraction by two operative approaches, 23 done through the intrahepatic duct stump (RBD-IDS, the RBD-IDS group) after partial hepatectomy and 12 through the hepatic parenchyma by retrograde puncture (RBD-RP, the RBD-RP group). The gallbladders were preserved and the common bile duct (CBD) incisions were primarily closed. The patients were examined postoperatively by direct cholangiography and followed up by ultrasonography once every six months. RESULTS: In the RBD-IDS group, residual bile duct stones were found in three patients, which were cleared by a combination of fibrocholedochoscopic extraction and lithotripsy through the drainage tracts. The tubes were removed on postoperative day 22 (range: 16-42 days). In the RBD-RP group, one patient developed hemobilia and was cured by conservative therapy. The tubes were removed on postoperative day 8 (range: 7-11 days). Postoperative cholangiography showed that all the gallbladders were well opacified, contractile and smooth. During 54 (range: 6-120 months) months of follow-up, six patients had mildly thickened cholecystic walls without related symptoms and further changes, two underwent laparotomies because of adhesive intestinal obstruction and gastric cancer respectively, three died of cardiopulmonary diseases. No stones were found in all the preserved gallbladders. CONCLUSION: The intact gallbladders preserved after surgical extraction of primary bile duct stones will not develop gallstones. Retrograde biliary drainage is an optimal approach for gallbladder preservation. (+info)
Selective cholangiography. Current role in laparoscopic cholecystectomy.
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The initial 22-month experience with laparoscopic cholecystectomy in 400 patients employing an algorithm of selective cholangiographic evaluation is reported. Preoperative or postoperative endoscopic retrograde cholangiography was performed whenever stones were suspected clinically. Preoperative endoscopic retrograde cholangiography was performed in 44 patients (11%), in whom 14 (3.5%) had an endoscopic sphincterotomy with extraction of common bile duct stones. Intraoperative cholangiography was performed in only eight patients (2%) almost exclusively to acquire experience with the technique, and all cholangiograms were normal. Laparoscopic cholecystectomy was successfully completed in 96% of the patients. There were no deaths in this series, and major complications occurred in only 5% of patients. Two patients (0.5%) had a significant common bile duct injury that was recognized and successfully repaired at the initial operation. No late common bile duct strictures have been recognized. Six patients (1.5%) underwent postoperative endoscopic retrograde cholangiography for suspected common bile duct stones, with three patients requiring endoscopic sphincterotomy and stone extraction. This experience suggests that the use of preoperative and postoperative endoscopic retrograde cholangiography can be based on clinical presentation and laboratory evaluation and does not need to be performed routinely. Routine intraoperative cholangiography is not necessary in most patients undergoing laparoscopic cholecystectomy. The authors conclude that laparoscopic cholecystectomy can be performed safely with the selective use of cholangiography. (+info)
THE DIAGNOSTIC VALUE OF SERUM LEUCINE AMINOPEPTIDASE.
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Serum leucine aminopeptidase determination was found to be a useful screening procedure for hepatobiliary disease in jaundiced and unjaundiced patients. Values under 1,000 units are of no help in the differential diagnosis of jaundice but values above 1,000 units are highly indicative of biliary obstruction. The differentiation of intra- from extrahepatic obstruction as well as of malignant from benign jaundice cannot generally be established by this single test. (+info)