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Functional gradients in muscle cells isolated from gallbladder, cystic duct, and common bile duct.

The existence of a gradient inherent to muscle cells of the biliary tract was examined in muscle cells isolated separately from the fundus of the gallbladder, cystic duct, and common bile duct of the dog. Muscle cells, measured in suspension or as single perfused cells, exhibited a proximal-to-distal gradient expressed by the magnitude of response and the sensitivity to hormonal cholecystokinin octapeptide and neural (acetylcholine and methionine-enkephalin) contractile agonists. Measurements in suspensions showed that cells from the fundus 1) were 7-40 times more sensitive to contractile agonists than cells from the cystic duct and 13-200 times more sensitive than cells from the common bile duct and 2) generated greater maximal contraction. The latter was expressed by the ratio of maximal responses (fundus: cystic duct cells, 1.90 +/- 0.12, P less than 0.001; fundus: common bile duct cells, 1.50 +/- 0.07 P less than 0.001), which was independent of sensitivity to agonists. Similar results were obtained in measurements on single cells with respect to relative sensitivity and to ratio of maximal responses (fundus: cystic duct cells, 1.80 +/- 0.08, P less than 0.001; fundus: common bile duct cells, 1.49 +/- 0.06, P less than 0.001). The ratio of responses to low concentrations of agonists was even higher (three- to fourfold), reflecting both the greater sensitivity and the greater contraction of muscle cells of the fundus. We conclude that a proximal-to-distal biliary gradient exists that is an inherent property of muscle cells from various regions of the biliary tract; the gradient would act to facilitate gallbladder emptying in response to hormonal and neural stimulation.

Acetylcholine↗

A tissue-engineered artificial bile duct grown to resemble the native bile duct.

The aim of this study was to fabricate an artificial bile duct for the development of a new treatment for biliary diseases. Eighteen hybrid pigs were implanted with a bile duct organoid unit (BDOU) made of a bioabsorbable polymer. Twelve of the transplanted BDOUs had been seeded with autologous bone marrow cells (BMCs) in advance. Six animals, the controls, were grafted with the scaffold alone with no BMCs seeded. The common bile duct was cut, the hepatic cut end of the native common bile duct was anastomosed to the BDOU and the other end was anastomosed to the duodenum. The controls underwent a similar operation. The neo-bile duct was removed at pre-determined time points and investigated histologically. All 18 recipient pigs survived until their sacrifice at 6 weeks, 10 weeks or 6 months. Histological examination revealed incomplete epithelialization of the neo-bile duct at 6 weeks and 10 weeks after transplantation. At 6 months, the organoid exhibited a morphology almost identical to that of the native common bile duct. No differences were found between the controls and BMC-seeded pigs. These results show that the artificial bile duct thus fabricated can serve as a substitute for the native bile duct.

Absorbable Implants↗

[Transient dilatation of the intra- and extra-hepatic bile ducts. A new aspect of bile duct involvement in scarlet fever].

An extra- and intra-hepatic bile duct dilatation has been observed in a child in the course of scarlet fever. Manifestations of cholestasis, cytolysis and inflammation were present. Pruritus disappeared within 2 months, biological abnormalities within 3 months and ultrasonic bile duct abnormalities between 3 and 6 months, with a follow-up of 9 months. This case report suggests a relationship between a transitory obstruction, possibly toxic in origin, of the bile ducts and the scarlet fever.

Bile Ducts, Intrahepatic↗

Reconstruction after subtotal duodenopancreatectomy in patients with pancreatic duct, distal bile duct and ampullary carcinoma: further experience with a personal technique.

A total of 142 patients underwent pancreatic resection for malignant (128 patients) or benign (14 patients) pancreatic disease. Of these patients, 111 had subtotal duodenopancreatectomy and are discussed in this paper. Reconstruction in these patients was carried out with a special technique. In this technique, two jejunal loops are used. One for fashioning the gastric anastomosis, the other for fashioning the pancreatic and biliary anastomosis. Two patients died in the first 30 postoperative days. Twenty patients had severe complications necessitating early reoperation. The surviving patients had a good quality of postoperative life. Postoperative sequelae like diabetes, steatorrhea and motility disturbances were easily controllable. On the basis of the results obtained, the reported surgical technique of reconstruction of alimentary continuity after subtotal duodenopancreatectomy can be considered an alternative for the surgical management of some of the patients with malignant or benign pancreatic disease considered eligible for subtotal duodenopancreatectomy.

Ampulla of Vater↗

Expression of epithelial-cadherin, alpha-catenin and beta-catenin during human intrahepatic bile duct development: a possible role in bile duct morphogenesis.

BACKGROUND/AIMS: Cell adhesion molecules play an important role in the morphogenesis of developing organs. However, little is known about their expression during intrahepatic bile duct development. METHODS: We immunohistochemically investigated the expression of E-cadherin (E-Cad), alpha-catenin (A-Cat) and beta-catenin (B-Cat) during human intrahepatic bile duct development, using 31 fetal livers of various gestational ages. The developmental stages of bile ducts were classified into the ductal plate, migrating biliary cells (remodeling stage), and immature bile ducts (remodeled stage). RESULTS: E-Cad was broadly and strongly expressed in the ductal plate with a cytoplasmic pattern, heterogeneously and weakly expressed in the migrating biliary cells with a cytoplasmic pattern, and broadly and strongly expressed in immature bile ducts with a membranous pattern. A-Cat was broadly and strongly expressed in the ductal plate with a membrane pattern, broadly and moderately expressed in the migrating biliary cells with a membranous pattern, and broadly and strongly expressed in immature bile ducts with a membranous pattern. In contrast, expression of B-Cat was weak or slight in the ductal plate, but B-Cat was expressed broadly and strongly with a membranous pattern in migrating biliary cells and in immature bile ducts. Immature hepatocytes rarely expressed E-Cad and A-Cat, but expressed B-Cat with a membranous pattern throughout development. CONCLUSIONS: These results suggest that E-Cad, A-Cat and B-Cat are involved in the normal developmental morphogenesis of human intrahepatic bile ducts.

Bile Ducts, Intrahepatic↗

Pancreatic lipase is a useful phenotypic marker of intrahepatic large and septal bile ducts, peribiliary glands, and their malignant counterparts.

Expression of pancreatic lipase in normal, proliferating, and carcinomatous epithelia of the intrahepatic biliary tree was examined by immunohistochemistry in 82 normal livers, 35 hepatolithiatic livers, 11 cholangiocarcinomas (CCs) associated with hepatolithiasis, 34 CCs, and four combined hepatocellular-cholangiocellular carcinomas. The intrahepatic biliary tree was anatomically divided into large ducts, septal ducts, interlobular ducts, bile ductules, and peribiliary glands. In hepatolithiasis, large ducts, septal ducts, and peribiliary glands showed marked proliferation and dysplasia. In normal livers and hepatolithiasis, expression of pancreatic lipase was found in large ducts in 91% and 94%, in septal ducts in 95% and 94%, and in peribiliary glands in 93% and 94%, respectively. Interlobular ducts, bile ductules, and hepatocytes were negative for pancreatic lipase. The immunoreactivity of pancreatic lipase was coarse granular, and was regularly present in the supranuclear and to a lesser degree paranuclear cytoplasm of the epithelial cells. All cases of CCs with hepatolithiasis, which arised from large ducts, expressed pancreatic lipase. In CCs, pancreatic lipase was expressed in the perinuclear cytoplasm of cancer cells in 67% in the hilar type and in 24% in the peripheral type (P < 0.02). The combined hepatocellular-cholangiocellular carcinomas failed to express pancreatic lipase in both elements. These data suggest that large ducts, septal ducts, and peribiliary glands contain pancreatic lipase in normal and proliferative conditions, and that CCs probably arising from these ductal elements continue to express pancreatic lipase. Thus, pancreatic lipase could be a phenotypic marker of large ducts, septal ducts and peribiliary glands as well as their malignant counterparts.

Adenoma, Bile Duct↗

Effect of ursodeoxycholic acid administration on bile duct proliferation and cholestasis in bile duct ligated rat.

The origin, mechanism, and significance of the bile duct proliferation (BDP) associated with cholestasis remain unexplained. This study examined the effect of oral administration of ursodeoxycholic acid (UDCA) on both BDP and cholestasis in the rat. After bile duct ligation, male Sprague-Dawley rats were treated for 30 days with either UDCA (5 mg/day) (group A) or saline solution (group B). Animals were sacrificed at day 30. The serum activity of aminotransferase (ALT, AST), alkaline phosphatase, and gamma-glutamyltransferase (GGT) was significantly lower (P < 0.01) in the UDCA-treated rats. Total serum bilirubin and total serum bile acids were lower (P < 0.001) in group A. Moreover, the control of BA in bile was reduced also (P < 0.02). Conversely, serum cholesterol levels were not different between the two groups. Histological examination showed that the number of ductular cells in the portal areas was significantly (P < 0.001) reduced in UDCA-treated as compared to saline-treated rats. The replication activity, assessed as the number of bromodeoxyuridine-positive cells, was also significantly lower in treated animals (33 +/- 11 vs 64 +/- 22 per 1000 cells; P < 0.001). Lobular bile ductules were three times larger in group B, and extrahepatic duct measurements confirmed this increase in size of the larger biliary ducts (P < 0.001). These findings demonstrate that UDCA reduces BDP in response to BD ligation. Although the mechanism(s) of this effect is still hypothetical, UDCA may reduce the level of irritating bile salts such as chenodeoxycholic acid and lithocolate and increase periductular bile acid recirculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Papillary carcinoma of the common bile duct. Diagnosis by bile drainage cytology.

A 54-year-old man with clinical and radiologic findings suggestive of pancreatic carcinoma had cytologic examination of bile drainage fluid specimens prepared by membrane filtration and cytocentrifugation. Examination showed clumps of malignant cells with features most consistent with a well-differentiated papillary neoplasm of bile duct origin, rather than a primary pancreatic carcinoma. Partial pancreatoduodenectomy with resection of the proximal common bile duct confirmed the presence of a small, well-differentiated but invasive papillary bile duct carcinoma. Pancreatic carcinoma and papillary carcinoma of the bile duct are anatomically and biologically different lesions that should be distinguished, when possible, by cytologic examination. In this case, surgical treatment was planned on the assumption that cytologic examination could distinguish a papillary carcinoma of the bile duct from the clinically suspected pancreatic adenocarcinoma.

Adenocarcinoma↗

Risk of bile duct carcinogenesis after excision of extrahepatic bile ducts in pancreaticobiliary maljunction.

BACKGROUND: A reflux of pancreatic juice into the biliary tract caused by pancreaticobiliary maljunction (PBM) has been considered important in the development of biliary tract carcinogenesis in choledochal cysts. We excised extrahepatic bile ducts in patients with choledochal cysts to terminate the reflux of pancreatic juice. We investigated whether this surgery could stop the development of the residual bile duct carcinoma. METHODS: Fifty-six patients with a diagnosis of PBM with choledochal dilatation underwent surgical excision of extrahepatic bile ducts. We applied a person-year method to compare the relative risks (observed number/expected number) of biliary tract carcinoma before and after surgery. RESULTS: In 3 patients, bile duct carcinoma developed in residual dilated segments 19 years 6 months, 8 years 8 months, and 2 years 5 months, respectively, after surgery. Although the relative risk in the post-surgery group was slightly decreased by surgery, it was still high compared with that of the general population. CONCLUSIONS: The incidence of bile duct carcinoma is still high, even after excision of extrahepatic bile ducts in PBM patients with choledochal dilatation. For these patients, careful long-term follow-up is necessary, especially after operations that leave the dilated bile ducts, such as cases of Todani's type IV-A.

Adolescent↗

[A case of duplication of the common bile duct with anomaly of the intrahepatic bile duct].

A 50-year-old man, with a complaint of fever and epigastralgia, was admitted to the Yamaga City Hospital. Choledocholithiasis and stenosis of the lower part of choledochus were pointed out. Cholecystectomy, choledocholithotomy and papilloplasty were performed and the choledochotomy closed over a T-tube. T-tube cholangiograms, after operation, revealed stenosis, negative shadow and abnormal branching of the left intrahepatic bile duct. Then, the lateral segmentectomy of the liver was done. But the negative shadow didn't disappear . With further examination, we could find the accessory bile duct in the retroperitoneal space. Cholangiogram, from this accessory bile duct, revealed patency of this bile duct into the left intrahepatic bile duct and the duodenum. A final diagnosis of duplication of the common bile duct was established. We collected Japanese cases of this anomaly and discussed a classification of the disorder.

Abnormalities, Multiple↗

Restoration of bile ducts in drug-induced vanishing bile duct syndrome due to zonisamide.

Prolonged drug-induced cholestasis may be due to destruction and disappearance of bile ducts, sometimes referred to as vanishing bile duct syndrome. Although some of these cases progress to fibrosis, cirrhosis, and liver failure, others improve with time. We report a case of a 35-year-old man who developed vanishing bile duct syndrome after ingestion of zonisamide, an antiepileptic drug that is also prescribed for weight loss. His liver biopsy showed complete absence of bile ducts 3 weeks after starting treatment. There was no ductular reaction. The drug was stopped and a follow-up biopsy 3 months later showed strands of intermediate hepatobiliary cells at the periphery of the portal tracts that extended into lobules; these structures lacked lumina and expressed biliary cytokeratins, CK7 and CK19. A third biopsy, 7 months later, showed the presence of ductules with lumina located within portal tracts. Intermediate hepatobiliary cells were rare; although sparse clusters of hepatocytes with membrane staining for CK7 were present. Cholestasis and levels of bilirubin improved over time. The histologic features in this case document the sequence of events in restoration of the biliary tree after loss of bile ducts, which seems to be a process of maturation of intermediate hepatobiliary cells that arise from a proliferative compartment at the porto-hepatic interface.

Adult↗

Rejection of murine congenic bile ducts: a model for immune-mediated bile duct disease.

Immune-mediated injury of prenatal and postnatal extrahepatic bile duct epithelium has been poorly characterized. In a transplantation model of bile duct allografts, segments of the common bile duct from fetal day 18, postnatal day 7 and day 21, and adult (greater than 6-weeks) mice were grafted under the renal capsule of adult congenic mice. The progression of rejection injury in these bile duct allografts was then followed by histological evaluation at 1-week intervals. After 3 weeks there was a significant difference in the number of fetal congenic bile duct grafts that had maintained their luminal architecture compared with the more mature adult congenic grafts that had fibrosclerosed. The onset and progression of the rejection injury in the adult congenic bile duct grafts was associated with an induction of class I and class II histocompatibility antigen expression in the adult bile duct epithelium; the severity of this injury could be attenuated by treatment of the recipient mice with cyclosporin A. Thus, the fibrosclerosing lesion of extrahepatic ducts observed in this model of rejection injury is similar to the histopathology of neonatal biliary atresia or primary sclerosing cholangitis, and susceptibility to this injury is dependent on the age of the donor tissue. The immune nature of the injury and the ontogeny of expression of histocompatibility antigen in bile duct tissue indicate that the above factors may be important to the pathogenesis of these extrahepatic bile duct diseases. This experimental model may be used to test for novel factors that may modulate immune responses directed against extrahepatic bile duct epithelium.

Animals↗