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Whether or not prophylactic excision of the extrahepatic bile duct is appropriate for patients with pancreaticobiliary maljunction without bile duct dilatation.

BACKGROUND/AIMS: The standard treatment for patients with a pancreaticobiliary maljunction (PBM) without bile duct dilatation remains controversial. METHODOLOGY: We followed up 29 patients with such PBM who mainly underwent a cholecystectomy alone. The ages of the patients ranged from 3 to 76 years (average age 47.3 years) and the ratio of males to females was 8 vs. 21. When the diameter of the common bile duct was less than 10mm, such bile ducts were diagnosed to have no dilatation. The main clinical indications for surgery were cholecystolithiasis in 15 patients, choledocholithiasis in 3, cholecystocholedocholithiasis in 2, gallbladder polyp in 2, adenomyomatosis in 2, cholecystitis in 2, and protein plug in 1. RESULTS: The amylase levels of gallbladder bile in 20 patients ranged from 115 to 460,200 IU/mL (a mean of 191,698 IU/mL). One patient died of gastric cancer 182 months after surgery and two patients died of other diseases 153, 171 months after surgeries, respectively. The remaining 26 patients have all been doing well for 36 months to 326 months after surgery (a median follow-up period, 160.5 months). The 10- and 15-year survival rates were 100% and 89.7%. CONCLUSIONS: In conclusion, a prophylactic resection of the extrahepatic bile duct and biliary diversion could be unnecessary for patients with PBM without bile duct dilatation.

Adolescent↗

Is preventive resection of the extrahepatic bile duct necessary in cases of pancreaticobiliary maljunction without dilatation of the bile duct?

BACKGROUND: No consensus has been reached on whether preventive resection of the extrahepatic bile duct is necessary in cases of pancreaticobiliary maljunction (PBM) without dilatation of the extrahepatic bile duct (undilated type). METHODS: Sixty-eight patients with PBM underwent corrective surgery and several clinical characteristics and pathological findings including K-ras point mutation were evaluated. RESULTS: Unlike dilated bile duct, none of the patients with undilated type duct had clinical symptoms in early childhood. In patients with either cystic or spindle type duct, amylase levels in the bile duct were >10(4) U/l, whereas those in patients with undilated type duct were <10(4) U/l. Postoperative scintigraphy of the biliary system of undilated type revealed no evidence of cholestasis. After surgery, eight patients with undilated type duct, in whom the bile duct had been preserved, had no further clinical symptoms and no evidence of malignancy. Bile duct tissue specimens revealed no hyperplasia, dysplasia or cancerous lesions and they had no K-ras mutation in undilated type. CONCLUSION: The results showed that there was little bile stasis, injury to the mucosa was mild and less genetic changes could be seen in patients with undilated type duct. Therefore, in patients without dilatation of bile duct and advanced cancer, cholecystectomy alone is sufficient.

Adult↗

Connection of ductlike structures induced by a chemical hepatocarcinogen to portal bile ducts in the rat liver detected by injection of bile ducts with a pigmented barium gelatin medium.

Newly found metaplastic ductlike structures that form in the liver of rats exposed to carcinogens are connected to preexisting bile ducts. Male Fischer rats fed a diet of N-2-acetylaminofluorene in a choline-deficient diet (CDAAF) develop a massive proliferation of oval cells which appear to differentiate into bile-ductlike structures. However, unlike normal or proliferating bile ducts, these ductlike structures contain alpha-fetoprotein (AFP) and albumin, which are markers for proliferating hepatocytes and some hepatocellular carcinomas. Bile duct injections with a green pigmented barium gelatin medium filled the lumens of the ductlike structures and typical ductlike structures induced by the CDAAF diet, as well as the proliferating bile ducts induced by the noncarcinogenic alpha-naphthylisothiocyanate (ANIT), and the ducts in the normal controls. AFP was present in the ductlike structures in the rats fed AAF, but not in the bile ducts of animals fed ANIT. These studies suggest that most, if not all, of the ductlike structures produced during chemical hepatocarcinogenesis are derived from bile ducts, yet have the capacity to produce AFP and albumin.

2-Acetylaminofluorene↗

Induction of rat liver alkaline phosphatase: the mechanism of the serum elevation in bile duct obstruction.

Bile duct ligation in the rat leads to a rapid increase in hepatic and serum alkaline phosphatase activity. Within 12 hr after bile duct ligation, hepatic alkaline phosphatase has increased 7-fold and serum alkaline phosphatase activity 2(1/2)-fold. The elevation in the serum activity is completely due to an increase in an isozyme that appears to originate in the liver. This serum isozyme and liver phosphatase, both partially purified by DEAE-cellulose column chromatography, have identical Michaelis constants, pH optima, and rates of heat denaturation. These isozymes migrate identically when subjected to electrophoresis on polyacrylamide gel, and their migration rates are equally slowed after neuraminidase digestion. The data suggest that the rise in hepatic alkaline phosphatase activity is dependent on de novo protein synthesis. Cycloheximide, in a dose that inhibited incorporation of leucine-(14)C into protein by 68%, inhibited the rise in liver phosphatase by 98% and that in serum by 80%. The rise in liver phosphatase activity could not be accounted for by simple retention of alkaline phosphatase that would normally appear in bile. The rise in liver activity after bile duct ligation was 240 times greater than the amount of phosphatase that normally appears in bile over a similar period of time. Cycloheximide had no effect on the bile duct ligation-induced changes in the serum and liver glutamic pyruvic transaminase.

Alanine Transaminase↗

[Reoperations on the extrahepatic bile ducts after surgery of the common bile duct or its indirect drainage].

An analysis is made of 80 re-interventions on the extra-hepatic biliary pathways in patients who had underwent one or more surgical interventions on the main biliary pathway. The cases have been classified according to the type of the initial intervention as follows: re-interventions following cholecystectomy, choledocotomy and Kehr drainage, following sphincterotomy, and following internal and external biliary derivations. An analysis is made of the causes of re-interventions, and of the increased risk due to severe complications which are at the origin of high morbidity and mortality rates. Particular stress is laid on the necessity for a correct diagnosis, as well as a complete one for the first intervention on the biliary pathways, which will allow to make an adequate choice for a second surgical solution.

Adult↗

Histological analysis of liver parenchyma and choledochal wall, and external diameter and intraluminal pressure of the common bile duct in controls and patients with common bile duct stones with and without acute suppurative cholangitis.

The purpose of this prospective controlled study was to determine the changes in intraluminal pressure and diameter of the common bile duct in a total of 121 bile patients with choledocholithiasis, and the consequences of these alterations for choledochal mucosa and liver histology. In fact, the reflux of bacteria from the obstructed biliary tract into the bloodstream is responsible for producing the clinical syndrome of acute suppurative cholangitis. Group I (26 patients) served as controls, Group II (50) had choledocholithiasis with clear green bile, and Group III (45) were patients with acute suppurative cholangitis with pus in the biliary tract. Ultrasonography revealed gallstones in all the patients. The external diameter of the common bile duct in patients with choledocholithiasis and acute suppurative cholangitis was significantly greater than in those of the other groups. Patients with acute suppurative cholangitis also had a higher intraluminal pressure than those of Groups I or II.

Acute Disease↗

Prognosis and treatment of bile duct carcinoma.

Bile duct carcinomas present a therapeutic challenge because of different histologies, tumor locations, and resectabilities. The goal of our study was to identify prognostic factors to better delineate therapeutic options. Forty patients (30 males and 10 females) diagnosed with bile duct cancer, treated between 1985 and 1996, at Kaiser Permanente Medical Center, Los Angeles were retrospectively reviewed. Three prognostically significant variables were identified: tumor histology, tumor location, and resection. Papillary histology was the most significant determinant of long-term survival. Of six patients with papillary adenocarcinoma, four patients (67%) underwent resection, with all four achieving long-term survival. Lower-third lesions also demonstrated a survival advantage. Four out of 12 (33%) lower-third tumors were resected, with a median survival of 36 months. Irrespective of tumor histology or tumor location, tumor resection always afforded longer survival times than did palliative treatments. A prognostic classification system based on weighted values of significant variables is presented that accurately predicted long-term survival. In conclusion, bile duct tumors in general are incurable, except perhaps for a small subset of patients with papillary adenocarcinoma. Papillary histology is the most significant determinant of ultimate survival and cure. A multifunctional prognostic classification system can be helpful for this perplexing disease.

Adenocarcinoma↗

Postoperative bile duct strictures.

Bile duct strictures are an uncommon but serious complication of primary operations on the gallbladder or biliary tree. Most strictures occur as a result of injury to the bile duct during cholecystectomy. In addition, strictures can occur at the site of previous biliary anastomoses for reconstruction of the biliary tree. Most patients with benign bile duct strictures present soon after their initial operation; however, in some cases, presentation is delayed for years. Cholangiography is essential for defining the anatomy of the biliary tree prior to management. In many cases, nonoperative biliary drainage is useful to treat sepsis and biliary fistulas. A number of alternatives exist for elective repair of bile duct strictures. Experience would suggest, however, that a choledochojejunostomy or hepaticojejunostomy performed through a Roux-en-Y limb of jejunum is the preferable management in most cases. Postoperative biliary stenting may be valuable in optimizing the results. Nonoperative management by percutaneous transhepatic or endoscopic balloon dilatation has been reported to be successful in a number of small series. Long-term results are limited, however. Comparative data suggest that surgical repair for benign postoperative strictures is associated with fewer long-term problems and with similar overall morbidity and costs.

Bile Ducts↗

[Bile-duct-stenosis after operation of the common bile-duct with T-tubes (author's transl)].

3 stenosis of the bile duct were observed in a postoperative study out of 25 patients, who underwent operations of the bile-duct-system and had T-tubes. These patients had no complaints. One patient had a reanastomosis of the bile duct, the stenosis was in the area of the anastomosis. The T-tubes of 2 patients were postoperatively under traction, which might have favoured the stenosis. The possibilities of intravenous cholangiography and endoscopic-retrograde cholangiography are discussed.

Biliary Tract↗

Ursodeoxycholate further increases bile-duct cell proliferative response induced by partial bile-duct ligation in rats.

BACKGROUND: Bile salts (BSs) stimulate cholangiocyte proliferation in vitro and in vivo in normal rats. In this study, we evaluated the effects of BS-enriched diets on cholangiocyte proliferative activity already triggered by partial bile-duct ligation (pBDL), a surgical model that induces mild cholestatic conditions, focusing our attention on ursodeoxycholate (UDC). METHODS: Animals (n=45) were fed either a standard diet, or a 0.2% deoxycholate- or 0.2% UDC-enriched diet for 4 weeks. Then, in each group, ten animals underwent pBDL and five underwent sham operation. Serum and biliary BS levels, serum cholestasis and cytolysis indexes, as well as liver conventional histology, apoptosis and proliferative activity were evaluated 48 h after the operation. RESULTS: Animals that underwent pBDL showed sustained proliferative response compared with sham-operated rats. BS-enriched diets did not influence cholangiocyte proliferation in sham-operated rats. However, significantly increased proliferation was observed in pBDL rats fed a UDC-enriched diet. The evaluation of humoral and histological parameters excluded the possibility that the increased proliferation induced by UDC-enriched diet could be related to concomitant liver cell damage. CONCLUSION: A UDC-enriched diet is able to amplify the magnitude of the cholangiocyte hyperplastic process, which occurs by a stimulatory mechanism after partial bile-duct ligation.

Administration, Oral↗

Characterization of cytosolic Ca2+ signaling in rat bile duct epithelia.

Bile duct epithelia play an important role in the formation and conditioning of bile. However, hormonal responses in this epithelial tissue are incompletely understood. Secretin increases ductular secretion through the intracellular messenger adenosine 3',5'-cyclic monophosphate (cAMP), but whether hormones increase cytosolic Ca2+ (Ca2+(i)) in these cells and whether Ca2+(i) regulates duct secretion is unknown. To address these questions, we examined Ca2+(i) signaling in isolated rat bile duct units using ratio microspectrofluorometry and confocal microscopy. We also used videomicroscopy to examine secretion and cell volume in isolated bile duct cells and duct units. Acetylcholine (ACh) and ATP both increased Ca2+(i) in bile duct units and elicited patterns of Ca2+(i) increases and oscillations that were distinct and dose dependent. In contrast, Ca2+(i) was not increased by the hepatocyte Ca2+(i) agonists vasopressin, angiotensin, and phenylephrine or by the exocrine pancreas agonists cholecystokinin (CCK) and bombesin. In addition, secretin did not increase Ca2+(i) in the isolated bile duct units, whereas ACh did not increase Ca2+(i) in isolated hepatocytes. Mobilization of internal, thapsigargin-sensitive Ca2+ stores contributed more than influx of extracellular Ca2+ to the Ca2+(i) increases induced in the duct units, and ATP-induced increases in Ca2+(i) could be blocked by microinjection of heparin but not de-N-sulfated heparin. ACh transiently decreased bile flow in the isolated perfused rat liver, although neither ACh nor ATP altered secretion in isolated ducts or changed the volume of single isolated bile duct cells. These findings demonstrate that bile duct epithelial cells possess both muscarinic and purinergic receptors that activate Ca2+(i) signaling pathways similar to those seen in other types of epithelia, but that the two types of receptors elicit distinct patterns of Ca2+(i) signals. Increases in Ca2+(i) have minimal direct effects on bile duct secretion, although it remains to be determined whether such signals selectively modulate other aspects of bile duct epithelial cell function.

Acetylcholine↗

Induction of rat liver alkaline phosphatase by bile duct ligation.

Bile duct ligation causes a five- to sevenfold increase in the activity of rat liver alkaline phosphatase within 12 hours after ligation and a similar rise in the activity of alkaline phosphatase in serum. The increased serum activity is due entirely to the appearance of a new isoenzyme that has the properties of rat liver alkaline phosphatase. The increase in both serum and liver alkaline phosphatase is prevented by the prior administration of cycloheximide in a dose that inhibits protein synthesis by 70%. Rat liver alkaline phosphatase was then purified to homogeneity. Antibody was raised to purified rat liver alkaline phosphatase in rabbits. The antibody was coupled to sepharose 4B and affinity columns made. (3)-H-leucine was then injected into the portal veins of sham operated rats and rats with bile duct ligation four hours after ligation. One hour after injection and five hours after ligation, animals were sacrificed. Liver alkaline phosphatase was purified by means of affinity chromatography and double immunoprecipitation with rabbit antibody to rat liver alkaline phosphatase and goat anti-rabbit gamma globulin. Bile duct ligation increased the incorporation of (3)-H-leucine into liver alkaline phosphatase more than threefold compared with sham operated rats, 164 CPM/mg protein vs. 49 CPM/mg protein (p < .001). The data indicate that the increased activity of rat liver alkaline phosphatase after bile duct ligation is due to enzyme induction rather than to activation of a pre-existing, relatively inactive enzyme.

Alkaline Phosphatase↗

Biliary peritonitis requiring reoperation after removal of T-tubes from the common bile duct.

BACKGROUND: Bile peritonitis can occur when a T-tube is electively removed from the common bile duct, but this is regarded as a rare complication. Plastic T-tubes are known to increase this risk and should not be used. Latex rubber T-tubes are preferred, but the peritonitis can still occur. METHODS: Prospective data were collected on 1375 patients who underwent common bile duct exploration between March 20, 1994 and March 20, 2003. RESULTS: Thirty-four (2.47%) patients experienced generalized bile peritonitis after T-tube removal from the common bile duct. Mean age was 63.65 years. In all cases, a soft silicon-coated latex rubber T-tube was placed into the bile duct. All T-tubes were removed 21 days after surgery. Thirty-four patients developed acute generalized biliary peritonitis immediately after T-tube removal and required urgent active intervention. The mortality rate was 5.9%, and the mean hospital stay was 14.6 days. CONCLUSIONS: The most common causes of lack of formation of T-tube tract and operative procedure were unknown and T-tube reinsertion, respectively. T-tube removal can result in significant morbidity and mortality.

Adult↗

[Mechanism of the bile duct dilatation in congenital dilatation of the common bile duct].

Radiographic studies including operative cholangiography, endoscopic retrograde cholangiopancreaticography and percutaneous transhepatic cholangiography were performed in 44 patients with congenital dilatation of the common bile duct. The relation between the maximum transverse diameter of the common bile duct (CBD) as an indicator of the degree of dilatation and various possible factors causing dilatation of CBD was studied. Among these factors, the length of the narrow segment (X) was closely related with the maximum transverse diameter (Y). The relation of these two was expressed by a simple equation; log Y = 0.068X + 1.06 (r = 0.934, p less than 0.001, n = 19) Dilatation of CBD has been successfully produced by narrowing the ductal lumen with a small plastic tube encirculating the distal common bile duct in dogs. Experimental dilatation was quite similar with congenital dilatation. In addition, the relation between the maximum transverse diameter (Y') and the length of the narrow segment (X') was also expressed in the following simple equation; log Y' = 0.060X' + 0.88 (r = 0.972, p less than 0.001, n = 18) The present studies did not support the hypothesis that abnormal junction of the pancreatico-biliary system might be the primary cause of congenital dilatation of CBD. They suggest that the stenosis of the distal CBD in the fetal life may determine dilatation of CBD.

Animals↗

Carcinoma of the common bile duct with superficial spread to the intrahepatic segmental bile ducts: a case report.

A 54-year-old woman presented with jaundice. Percutaneous transhepatic biliary drainage, cholangiography via a percutaneous transhepatic biliary, drainage catheter, and percutaneous transhepatic cholangioscopy were performed to alleviate the jaundice and to evaluate her biliary system. A diffuse-type tumor was detected in the common bile duct. The tumor had spread superficially up to the right anterior segmental duct and the left hepatic duct and involved the caudate branches. Curative surgery, which included a right anterior segmentectomy, total caudate lobectomy, and pylorus-preserving pancreatoduodenectomy, was performed. The histopathologic diagnosis was moderately differentiated tubular adenocarcinoma originating at the common bile duct. The extent of the superficial spread of the tumor corresponded to our preoperative determination. Her postoperative recovery was uneventful. In this case report, we discuss the accurate preoperative diagnosis and rational surgical treatment of bile duct carcinoma with superficial spread.

Adenocarcinoma↗