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PubMed1988

Common bile duct pressure in patients with common bile duct stones with or without acute suppurative cholangitis.

Resting common bile duct pressure was measured in three groups of patients: group 1, 53 patients with gallstones but without common duct stones; group 2, 35 patients with common bile duct stones unaccompanied by cholangitis; and group 3, 36 patients with common duct stones and acute suppurative cholangitis. A significantly higher pressure in the common bile duct was documented in patients with cholangitis when compared with the other two groups. Twenty-four patients with cholangitis had common duct pressure values above 20 cm H2O, the maximal values of normal. Additionally, patients with cholangitis with pressure values over 30 cm H2O (nine patients) showed absence of green bile in the extrahepatic biliary tract, suggesting cessation of bile excretion into biliary duct. In all these cases, an impacted stone at the distal end of the common bile duct was documented.

Acute Disease↗
PubMed1988

Effect of bile duct ligation on bile acid and cholesterol metabolism in rats.

The effects of bile duct ligation on bile acid and cholesterol metabolism were examined in male Wistar strain rats. Quantitative and qualitative changes of bile acids and cholesterol in serum and urine occurred; beta-muricholic acid predominantly increased in serum and urine and the ratio of urinary cholic acid and beta-muricholic acid changed from about 5:3 on day 1 to about 1:8 on day 5 under biliary obstruction. The form of the increased urinary bile acids was mainly taurine-conjugated and partly sulfated. Under conditions of bile duct ligation on day 5, 14C-labeled 3 beta-hydroxy-5-cholenoic, lithocholic, and chenodeoxycholic acids were intragastrically administered to the rats after pretreatment with antibiotics and the metabolites of these three acids were investigated. 3 beta-Hydroxy-5-cholenoic acid was most efficiently converted to beta-muricholic acid. The present study strongly suggested the presence of an alternative metabolic pathway induced by bile duct ligation, which caused the change in composition of urinary bile acids, and especially the marked increase in beta-muricholic acid formation. A possible alternative pathway for bile acid biosynthesis under biliary obstruction in rats is postulated.

Animals↗
PubMed2006

Intraductal papillary neoplasm of the bile duct extending superficially from the intrahepatic to extrahepatic bile duct.

Intraductal papillary neoplasm of the bile duct (IPNB) or liver is a recently noted rare disease, and its pathogenesis remains unclear. Here we present a case of IPNB with an interesting morphology, which was treated by resection of the right hemiliver and extrahepatic bile duct. A 79-year-old woman was found to have a high alkaline phosphatase level and slight dilatation of the right intrahepatic bile duct on imaging studies. The right intrahepatic bile duct became dilated over a 2-year period; however, no solid mass could be detected, and tumor markers were not elevated. Hepatic resection was scheduled because a mucin-producing bile duct carcinoma of the liver was suspected. A right hemihepatectomy was conducted, and the extrahepatic bile duct was also resected after malignant cells were found in the surgical stump of the right bile duct and in the bile itself. Macroscopically, diffuse dilatation of the intrahepatic bile duct was noted, but no solid component or mucin within the duct was found. Histopathological findings revealed carcinoma in situ, IPNB, in the majority of intrahepatic bile ducts, with no lymph node metastasis, and it extended continuously to the epithelium of the common bile duct. No tumor recurrence or biliary dilatation was observed at follow-up 2 years after surgery. It is important to consider malignancy in the presence of a dilated bile duct and in the absence of any cause of occlusion. Complete resection of IPNB results in a good prognosis and no recurrence.

Aged↗
PubMed2002

Inactivation of the INK4a/ARF locus and p53 in sporadic extrahepatic bile duct cancers and bile tract cancer cell lines.

The tumor-suppressor genes p14(ARF), p16(INK4a) and Tp53 are commonly inactivated in many tumors. We investigated their role in the pathogenesis of 9 bile tract cancer cell lines and 21 primary sporadic extrahepatic bile duct carcinomas. p53 and p16 protein expression was examined by Western blot analysis and immunohistochemistry. Mutation screening of p53 was done by SSCP and direct sequencing. Inactivating mechanisms of p14 and p16 were addressed by screening for mutations, homozygous deletions, chromosomal loss of 9p21 (loss of heterozygosity [LOH] analysis) and promoter hypermethylation of the p14/p16 genes. p53 overexpression could be detected in 7 of 9 cell lines and 7 of 21 primary tumors, but mutations were found in 3 cell lines only. p16 expression was absent in all cell lines, due to homozygous deletion of the gene in 8 of 9 cell lines and hypermethylation of the p16 promoter in one cell line (CC-LP-1). p14 exon 1beta was homozygously deleted in 6 of 9 cell lines, while retained in CC-LP-1 and 2 additional lines. No p14 promoter hypermethylation could be detected. p16 expression was lost in 11 of 21 primary tumors. p16 promoter hypermethylation was present in 9 of 21 primary tumors, all with lost p16 expression. Allelic loss at 9p21 was detected in 13 of 21 primary tumors, 10 of 11 with lost p16 expression and 8 of 9 with methylated p16 promoter. No p14 promoter hypermethylation or p14/p16 mutations could be detected. Neither Tp53 nor p16 alterations showed obvious association with histopathologic or clinical characteristics. In conclusion, inactivation of the p16 gene is a frequent event in primary sporadic extrahepatic bile duct cancers, 9p21 LOH and promoter hypermethylation being the principal inactivating mechanisms. Therefore, p16, but not p14, seems to be the primary target of inactivation at the INK4a locus in bile duct cancers. Other mechanisms than Tp53 mutations seems to be predominantly responsible for stabilization of nuclear p53 protein in bile duct cancers.

Bile Duct Neoplasms↗
PubMed1981

Effect of bile duct ligation on bile acid metabolism in rats.

The effect of bile duct ligation on the quantitative and qualitative changes of bile acids in serum, liver, urine, and feces, and the concentration of cholesterol and phospholipids in serum and liver were examined in male rats. The concentration of bile acids in serum increased over 100-fold on day 5 but was lower than the 5-day level on days 10 and 15. The concentration in the liver also increased about 10-fold. beta-Muricholic acid predominantly increased but the secondary bile acids, deoxycholic acid and hyodeoxycholic acid, decreased. The urinary excretion of bile acids increased to about 40 mg/day per rat on the first day of bile duct ligation but this increase was reduced on day 2 to about half and remained at that level until day 24. These values exceeded that of fecal bile acids, 12 mg/day per rat, before bile duct ligation. The amount of bile acid sulfates in the urine was as low as 1% of the total. The urinary non-sulfated bile acids consisted mainly of beta-muricholic acid (60%) and cholic acid (20%), while the sulfates contained a considerable amount of unidentified acidic substances (40%) in addition to cholic acid and beta-muricholic acid. The concentration of cholesterol and phospholipids in serum markedly increased on day 5 but declined gradually thereafter. The liver cholesterol concentration did not change but the phospholipid concentration decreased. Fecal sterols did not change in both the total amount and composition. These data indicated that daily synthesis of bile acids, especially beta-muricholic acid, was accelerated in bile duct-ligated rats.

Animals↗
PubMed2004

A case of benign bile duct stricture causing difficulty in differential diagnosis from bile duct carcinoma.

We report a patient with benign bile duct stricture causing difficulty in differential diagnosis from bile duct carcinoma. A 66-year-old woman consulted a local physician because of general fatigue. Blood biochemical tests showed increased levels of biliary tract enzymes. Abdominal ultrasonography (US) revealed tapering and blockage of the midportion of the bile duct and dilation of the intrahepatic bile ducts. Magnetic resonance cholangiopancreatography (MRCP) demonstrated obstruction of the midportion of the bile duct. Later, because a marked increase in biliary tract enzymes and jaundice appeared, percutaneous transhepatic biliary drainage (PTBD) was performed. Post-PTBD cytological examination of bile was negative for cancer. A third biopsy showed slight hyperplasia with no malignant findings. Recholangiography, performed through PTBD, suggested gradual improvement of bile duct stricture, but could not completely exclude the possibility of malignancy; thus, resection of the bile duct including the stricture site was performed, and the resected specimen was submitted for intraoperative frozen section examination. Histopathological diagnosis did not reveal malignant findings. After cholecystectomy and bile duct resection, hepaticojejunostomy (Roux-en-Y) was performed. Because only erosion and desquamation of the mucosal epithelium and mild submucosal inflammatory cell infiltration and fibrosis were observed, chronic cholangitis was diagnosed histopathologically. Surgical resection of the bile duct should be considered for potentially malignant stricture of the bile duct.

Aged↗
PubMed1992

Bile duct adenomas with endocrine component. Immunohistochemical study and comparison with conventional bile duct adenomas.

Bile duct adenomas are small nodules that are usually found incidentally on the liver surface at abdominal surgery or autopsy. We recently analyzed two such lesions that, in addition to the typical small caliber ducts, contained periductular nests and clusters of uniform round cells, suggestive of endocrine cell proliferation. Follow-up of these patients did not show endocrine tumors elsewhere. The lesions were studied by immunohistochemistry (avidin-biotin-peroxidase technique) and compared with conventional bile duct adenomas (seven cases). The results showed these cells to decorate with several endocrine markers, namely, neuron-specific enolase, chromogranin, synaptophysin, and Leu-7. Endocrine markers were not seen in the cells of conventional bile duct adenomas. Epithelial markers, that is, cytokeratin (CAM 5.2 antibody) and epithelial membrane antigen, were expressed by the cells composing both conventional bile duct adenomas and those with endocrine-like cells, although with less intensity in the endocrine cell clusters. We suggest that some bile duct adenomas contain endocrine cell proliferations that morphologically may resemble a small carcinoid tumor or the so-called pulmonary tumorlet. Neurosecretory granules have previously been identified in some cholangiocarcinomas and in bile duct proliferation associated with cholestasis. The endocrine clusters in biliary adenomas may constitute a diagnostic pitfall and must be separated from metastases of carcinoids or islet cell tumors.

Adenoma↗
PubMed1990

[A clinicopathological study of mucus producing bile duct carcinoma].

Bile duct carcinoma, which produces clinically recognizable mucus, was defined as "mucus producing bile duct carcinoma", and clinicopathological study was carried out in 7 cases of bile duct carcinoma suitable for the definition. All the tumors arose from the intrahepatic bile duct. There were no tumors arising from the extrahepatic bile duct. Superficially spreading mucosal infiltration of carcinoma was recognized in 6 cases out of 7, and accordingly distinct cholangiography after draining mucus through percutaneous transhepatic cholangio-drainage (PTCD) and percutaneous transhepatic cholangioscopy (PTCS) were indispensable for accurate diagnosis of the extent of carcinoma. The prognosis of patients with mucus producing bile duct carcinoma were almost satisfactory if rational operation had been performed according to accurate diagnosis. On the other hand, since mucus producing bile duct carcinoma frequently has a cystic lesion, the relation to biliary cystadenocarcinoma may become a subject of question. We advocate that biliary cystadenocarcinoma should be included in mucus producing bile duct carcinoma since biliary cystadenocarcinoma originally arises from the intrahepatic bile duct and very rarely from the extrahepatic bile duct. But now the concept of biliary cystadenocarcinoma is equivocal and further investigations will be requested.

Adult↗
PubMed2006

Difficult bile duct stones.

Bile duct stones are routinely removed at time of endoscopic retrograde cholangiopancreatography (ERCP) after biliary sphincterotomy with standard balloon or basket extraction techniques. However, in approximately 10% to 15% of patients, bile duct stones may be difficult to remove due to challenging access to the bile duct (periampullary diverticulum, Billroth II anatomy, Roux-en-Y gastrojejunostomy), large (> 15 mm in diameter) bile duct stones, intrahepatic stones, or impacted stones in the bile duct or cystic duct. The initial approach to the removal of the difficult bile duct stone is to ensure adequate biliary sphincter orifice diameter with extension of biliary sphincterotomy or balloon dilation of the orifice. Mechanical lithotripsy is a readily available adjunct to standard stone extraction techniques and should be available in all ERCP units. If stone extraction fails with these maneuvers, two or more bile duct stents should be inserted, and ursodiol added to aid in duct decompression, stone fragmentation, and stone dissolution. Follow-up ERCP attempts to remove the difficult bile duct stones may be performed locally if expertise is available or alternatively referred to a tertiary center for advanced extracorporeal or intracorporeal fragmentation (mother-baby laser or electrohydraulic lithotripsy) techniques. Nearly all patients with bile duct stones can be treated endoscopically if advanced techniques are utilized. For the rare patient who fails despite these efforts, surgical bile duct exploration, percutaneous approach to the bile duct, or long-term bile duct stenting should be discussed with the patient and family to identify the most appropriate therapeutic option. A thoughtful approach to each patient with difficult bile duct stones and a healthy awareness of the operator/endoscopy unit limitations is necessary to ensure the best patient outcomes. Consultation with a dedicated tertiary ERCP specialty center may be necessary.

Journal Article↗
PubMed2002

Laparoscopic transcystic bile duct stenting in the management of common bile duct stones.

BACKGROUND: The management of patients with common bile duct stones associated with stones in the gall bladder remains controversial. METHODS: Over the three-year period from 1996 to 1999, patients with cholelithiasis and known choledocholithiasis, or choledocholithiasis found at laparoscopic cholecystectomy, were initially treated by placing a stent across the sphincter of Oddi. The stent was pushed along a guide wire through the cystic duct and then down the common bile duct, before the cystic duct was closed. Subsequently, the stent was used to facilitate performance of a needle knife endoscopic sphincterotomy. The stent was then removed, a cholangiography was performed and the common bile duct was cleared. Patients with persistent jaundice usually had a preoperative endoscopic retrograde cholangio-pancreatography. RESULTS: Transcystic stenting was the 'intention-to-treat' basis of therapy for 56 of the patients. The placement of the stent only failed once when the stent became trapped in the cystic duct. Complications of the operation included: pain and jaundice (n = 2), cholangitis (n = 1), and pulmonary embolus (n = 1). The median postoperative hospitalization was 2 days (range: 1-15). Five further patients had common bile duct stones removed via a choledochotomy; a stent was placed through the choledochotomy before its closure. The selective common bile duct cannulation rate at the first endoscopic retrograde cholangio-pancreatography, was 98%. A second endoscopic retrograde cholangio-pancreatography was required in 15% of patients. The only complication of all the endoscopic procedures was a single case of mild cholangitis; there were no cases of pancreatitis. CONCLUSION: A treatment option open to all surgeons for non-jaundiced patients with known choledocholithiasis or choledocholithiasis found at operative cholangiogram, is the transcystic stenting of the sphincter of Oddi at the time of laparoscopic cholecystectomy. At a subsequent sitting, the common bile duct can be safely cleared endoscopically using a sphincterotomy facilitated by the stent.

Adolescent↗
PubMed1989

Long-term follow-up after choledochojejunostomy for bile duct stones with complex clearance of the bile duct.

In this retrospective study, the long-term follow-up of patients undergoing choledochojejunostomy (Roux-en-Y) for bile duct stones with complex clearance of the bile duct is evaluated. Bile duct exploration and subsequent choledochojejunostomy (Roux-en-Y) was performed in 43 patients (median age 67 years) in the period 1976-82. There was no mortality and only one patient had a major complication. Twenty patients died during follow-up (median follow-up period 5 years); the median follow-up period for the remaining 23 patients was 8 years. Good long-term results were found in 98 per cent of cases. No signs or symptoms could be related to bile duct obstruction or to cholangitis. Nearly all liver function tests and serum bilirubin levels were normal in the 21 patients who were tested. We conclude that patients with bile duct stones with complex clearance of the bile duct can be safely treated by means of a choledochoenterostomy (in this study a choledochojejunostomy Roux-en-Y).

Adult↗
PubMed1991

Primary "brown pigment" bile duct stones.

Bile duct stones from 42 patients were morphologically and chemically analysed. The calculi from 27 patients had important primary bile duct stone (PBDS) features, consisting of a general ovoid shape and fragile structure, with alternating light and dark brown pigmented layers on cross-section. Chemically these stones contained low levels of cholesterol, with high levels of bilirubin and calcium. Subsequent infrared spectroscopy analysis showed that calcium bilirubinate and calcium palmitate were the only calcium salts present. Calcium palmitate was prominent in the light brown layers. A morphological and chemical comparison with gallbladder stones showed that bile duct "stasis stones" were similar in morphological and chemical composition to the brown pigment gallbladder calculi. However, they were distinct from most gallbladder stones, indicating that primary bile duct calculi have an aetiology that is different to 90% of gallbladder calculi. Primary bile duct calculi were observed to occur with or without the presence of a gallbladder, and more interestingly, in the bile duct of two patients with cholesterol gallbladder stones. Bile duct bile of patients with primary choledocholithiasis were always moderately to profusely infected and with abundant calcium bilirubinate precipitation. Moreover, this study has shown that PBDS chemical analyses profiles were consistent and correlated well with their defined morphology. Consequently, PBDS may be accurately identified at the time of operation by morphology. An important aetiological factor would appear to be infection, which would seem to promote bile duct bile stasis and eventual stone growth.

Bile Duct Diseases↗
PubMed1993

Cancer of the gallbladder associated with anomalous junction of the pancreatobiliary duct system without bile duct dilatation.

The aim of this study was to delineate clinical features and prognosis of cancer of the gallbladder associated with anomalous junction of the pancreatobiliary duct system without bile duct dilatation, and to determine methods for managing the disease. A retrospective study of seven patients is presented. A further 27 cases from the Japanese literature were reviewed retrospectively with regard to method of treatment and prognosis. In 11 of 18 patients in whom staging was known the tumour was stage V, representing advanced disease. In seven of 34 cases curative operation was performed; only two patients survived for > 3 years. This poor outcome was due largely to delayed diagnosis of cancer of the gallbladder. Prophylactic cholecystectomy is recommended in patients with this anomalous junction without bile duct dilatation or a malignant lesion in the gallbladder, because of the high incidence of cancer of the biliary tract.

Adenocarcinoma↗
PubMed1995

Cholangiocarcinoma arising in bile duct adenoma with focal area of bile duct hamartoma.

A 59-year-old male with history of sigmoid colon cancer had a high serum-CEA level and was referred for the evaluation of metastatic liver disease. Ultrasonography and computerized tomography showed two tumours in the liver. Macroscopically, these were in segment 4 (S4) and 2 (S2). Histologically, the tumour in S4 showed a number of bile ductules with variable amounts of stroma, an appearance compatible with bile duct adenoma (BDA). There were markedly atypical ductules of various sizes, the epithelium of which had coarsely granular/hyperchromatic large nuclei, in some areas of the lesion. These atypical ductules showed invasive growth into the liver parenchyma. Some cystically dilated ductules with bile plugs resembling bile duct hamartoma (BDH) were also seen. The other tumour in S2, was a metastatic adenocarcinoma from sigmoid colon and showed strongly positive staining for CEA. Since the lesion in S4 of our case is solitary and most of histological features are similar to those of BDA with markedly atypical bile ductules, we consider that this may be the first case of cholangiocarcinoma associated with BDA with focal area of BDH. It is possible that the adenoma-carcinoma sequence occurs in biliary tumours.

Adenoma, Bile Duct↗
PubMed1983

[Suprapapillary instead of transpapillary bile duct drainage in proximal bile duct obstructions].

The transpapillary passage of a catheter for internal biliary drainage may produce complications due to reflux or acute pancreatitis. A review of 573 biliary obstructions due to malignant tumours showed that in half the obstruction lay in the proximal two-thirds of the biliary passages. Fibrous strictures are nearly always in this region. In these patients, suprapapillary instead of transpapillary internal biliary drainage can be used, thereby maintaining the physiological relationship in the papilla. For this purpose we use a specially designed catheter which meets the requirements of suprapapillary internal drainage.

Bile Reflux↗