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At least 19 recordsLinked to original sources
PubMed2025

EGFR activation in cholangiocytes promotes extrahepatic bile duct regeneration after injury.

BACKGROUND: The EGF receptor family of 4 tyrosine kinases, EGFR and ERBB2-4, and their ligands regulate the development and homeostasis of digestive organs including the hepatobiliary system. It promotes intrahepatic cholangiocyte proliferation, bile duct development, and cholangiocarcinoma aggressiveness. The EGF signaling network's contribution to extrahepatic bile duct (EHBD), which is a distinct hepatobiliary entity, regeneration is poorly defined. This work aimed to determine the fundamental role of the EGF signaling network in the biliary proliferative response to EHBD obstruction. METHODS: We used mouse bile duct ligation to model obstructive EHBD injury, and human and mouse EHBD organoids for in vitro studies. We tested activating and inhibitory paradigms with recombinant EGF family ligands and receptor antagonists. Transcriptomic and immunohistochemistry analyses informed EGF signaling changes and cellular localization at homeostasis and after obstruction. RESULTS: At homeostasis, the EHBD expressed EGFR ligands Tgfa, Btc, Hbegf, and Nrg4 in cholangiocytes, and Egf and Nrg2 in stromal cells. Erbb2 and Erbb3 were predominant receptors expressed in cholangiocytes, and Egfr in stromal cells at baseline. Post-injury, biliary hyperproliferation was associated with increased abundance of Tgfa, Btc, Hbegf, and Areg ligands and Egfr receptor in cholangiocytes with resulting EGFR activation. EGFR ligands induced biliary organoid growth, and inhibition of EGFR, not ERBB2, dampened organoid proliferation. EGFR inhibition in mice led to a decrease in the biliary proliferative response after EHBD obstruction. CONCLUSIONS: The obstruction-induced biliary proliferation is EGFR-mediated, suggesting context-specific and receptor-specific EGF signaling network contribution to EHBD regeneration after injury.

Animals↗
PubMed1978

Management of carcinoma of the extrahepatic bile ducts.

The records of 80 cases of carcinoma of the extrahepatic bile ducts were studied. The median duration of survival, in months, of patients who were treated by curative surgery, palliative surgery and radiation, palliative surgery alone and biopsy alone was 21.7, 9.3, 5.5 and 1, respectively. The best results were obtained by excision of the tumour, but only 10% of tumours were considered resectable. A more aggressive surgical approach to tumours still confined to the bile ducts might be expected to increase the resectability rate and improve survival. The use of a U tube is recommended because it ensures greater comfort even though survival is no longer than when a T tube is used. The roles of adjuvant radiotherapy and chemotherapy need further study. Because of some encouraging responses with the use of radiotherapy and the infusion of 5-fluorouracil the authors are currently evaluating these two methods of treatment.

Adenocarcinoma↗
PubMed1978

Topographic relation of portal vein to extrahepatic bile ducts. A combined portographic-cholangiographic study in 25 cadavers.

The extrahepatic course of both portal vein and bile ducts and their interrelation are analysed by simultaneous portography and cholangiography in 25 adult cadavers. The findings are correlated with the topographic anatomy in the porta hepatis, the hepatoduodenal ligament, and the duodeno-pancreatic region. Minor variations of the interspace between the bile ducts and the portal vein and superior mesenteric vein are demonstrated. The results of this investigation are discussed with respect to the clinical experience that carcinomas of the proximal part of the extrahepatic bile ducts often engage the bifurcation and the main stem of the portal vein, whereas the confluence of the portal vein and the superior mesenteric vein is more often affected by cancer of the head of the pancreas.

Adult↗
PubMed1978

[Surgical treatment of cancer of the extrahepatic bile ducts].

The authors present the 12 years' experience with the treatment of hepatocholedochal cancer (cancer of the supraduodenal end of the common bile duct and of the common hepatic duct included). 22 patients were operated upon. The authors managed to perform radical operations upon 5 out of 22 patients, when there were small tumors of the hepato-choledochus. The technic of operation and results of the treatment are described.

Bile Duct Neoplasms↗
PubMed1979

Histochemical studies of some hepatic enzyme activities in rat during extrahepatic common bile duct obstruction.

Studies on some enzyme activities as measured histochemically in the ligated common bile duct rat liver are reported. They show principally: an increased GGT reaction in the neoductular cells; a diffusion of the LAP reaction to the neoductuli; an immediate increase and diffusion of the alkaline phosphatase reaction; an increase of G-6-PA and AMPA reactions; an increase, during the first week, of the Phyla activity and a contemporary decrease of the UDPG-GS reaction. No significant changes have been observed in other enzyme activities. By means of some dehydrogenase reactions, morphological evidence that the hepatocytes may be involved in neoductular cells formation was obtained.

Adenosine Monophosphate↗
PubMedDate not supplied

Data regarding the structural feature of nervous elements in the bile ducts during intrauterine life.

The nervous elements of the extrahepatic bile ducts were studied on serial sections prepared from rabbit and human embryos and foetuses, using silver impregnation techniques. In the gallbladder of rabbit embryos and foetuses, the nervous elements are absent, whereas the bile ducts possess a dense parasympathetic vegetative plexus. In human embryos, the muscular layers and submucosa of the gallbladder and bile ducts have well developed parasympathetic plexuses and a sympathetic subserous plexus, without nerve cells, respectively. The histotopical identification of nervous elements in the bile ducts allows the distinction of parasympathetic plexuses from the sympathetic ones.

Adrenergic Fibers↗
PubMed1979

Percutaneous transhepatic portography in bile duct carcinoma. Correlation with percutaneous transhepatic cholangiography and angiography.

In 16 patients with carcinoma of the extrahepatic bile ducts, percutaneous transhepatic portography (PTP) and cholangiography (PTC) were performed. Fourteen of these patients also had angiography, which failed to show the tumor in 7 cases. Findings indicating non-extirpability of the tumor were demonstrated by angiography in 3 patients. At PTP non-extirpability was confirmed in these cases. PTP further indicated non-extirpability in one patient and gave hints of infiltration of the liver by the tumor in 5 patients because of intra or extrahepatic invasion of the portal vein.

Adenoma, Bile Duct↗
PubMed1976

Cyclic AMP in secretin choleresis. Evidence for a regulatory role in man and baboons but not in dogs.

Cyclic AMP output in the bile in response to intravenous secretin was measured in 11 patients, 12 baboons, and 15 dogs. Secretin was given to patients with bile drainage tubes as an intravenous bolus (1 U per kg). In baboons and dogs both secretin infusion (4 U per kg per hr) and bolus injection (1 U per kg) were used. In baboons cyclic AMP was also determined in liver, extrahepatic duct tissue, and in perfusate from isolated segments of extrahepatic bile ducts. Secretin induced a marked choleresis in all three species. In humans, biliary cyclic AMP concentration increased an average (+/- 1 SE) of 68% +/- 12% and in baboons 4-fold, but no increase occurred in dogs. In baboons, cyclic AMP concentration increased in both bile duct tissue and perfusate from isolated bile ducts concomitant with secretin choleresis, but not in liver. In humans the choleretic effects of sodium dehydrocholate, aminophylline, and glucagon were compared to dibutyryl cyclic AMP (DBcyclic AMP). All agents increased bile flow 2- to 3-fold. Cyclic AMP concentration in bile markedly increased after glucagon and DBcyclic AMP but not after sodium dehydrocholate and aminophylline. We conclude that cyclic AMP is implicated in secretin choleresis in both humans and baboons, but not in dogs. The bile duct appears to be the site of cyclic AMP elaboration induced by secretin in baboons and probably is also in man.

Aminophylline↗
PubMed1977

Common bile duct obstruction by hepatoma.

Two cases of hepatoma are presented in which the clinical manifestations of biliary obstruction resulted from growth of hepatoma into the extrahepatic bile duct. Recognition of such a manifestation of the hepatoma may allow for surgical extirpation of the tumor combined with radiation therapy, which may result in long survival.

Adult↗
PubMed1979

Bile duct obstruction in hepatocellular carcinoma (hepatoma)--clinical and cholangiographic characteristics. Report of 6 cases and review of the literature.

Direct cholangiography revealed 6 cases of hepatoma where tumor growth within the bile ducts caused obstructive jaundice. Characteristic features included bulky obstructing intraluminal masses in the proximal extrahepatic ducts. Distal common duct defects usually signify hemobilia and clots as tumor complication. Review of the literature disclosed only 22 cases in which common duct involvement was a predominant clinical feature. Hepatoma should be included in the different diagnosis of a cholangiographic filling defect in the proximal extrahepatic bile ducts. The recent widespread use of endoscopic and fine needle transhepatic cholangiography should aid in preoperative diagnosis.

Adult↗
PubMed1977

Congenital cystic dilatation of the common bile duct: relationship to anomalous pancreaticobiliary ductal union.

Thirty patients from 15 to 69 years of age with congenital cystic dilatation of the common bile duct were studied. The diagnosis was made by intravenous cholangiography in 70% of the patients and by percutaneous transhepatic cholangiography and/or endoscopic retrograde cholangiopancreatiography in the entire group. Cystic dilatation was also noted in the intraphepatic bile ducts in 12 patients. A union between the common bile and main pancreatic ducts occurred at a high position in 17 of 18 patients in whom both ducts were adequately opacified, forming an abnormally long common channel. One patient with choledochodele had a normal union. The anomalous unions were of two types: the pancreatic duct entering the common duct and the common duct entering the pancreatic duct. The mode of union was correlated with the degree of extrahepatic bile duct dilatation, age of onset, and frequency and severity of symptoms. It is postulated that the congenital anomaly in the union of the two duct systems is the cause of the disease and the congenital choledochocele has a different etiology.

Adolescent↗
PubMed1978

Computed tomographic diagnosis of obstructive jaundice in the absence of intrahepatic ductal dilatation.

Six patients with obstructive jaundice had computed tomography (CT) scans showing a dilated extrahepatic biliary tree in the absence of intrahepatic ductal dilatation. Dilated extrahepatic bile ducts were most easily identified by means of intravenous injection of urographic contrast material, which permitted them to be seen as low density structures. Findings in these patients emphasize that (1) demonstration of dilated intrahepatic bile ducts is not a prerequisite for the CT diagnosis of obstructive jaundice and (2) careful CT evaluation of the extrahepatic biliary tree is necessary to identify patients with isolated dilatation of the common hepatic or common bile duct.

Adult↗
PubMed1978

Percutaneous transhepatic intubation of bile ducts for combined internal-external drainage in preoperative and palliative treatment of obstructive jaundice.

Percutaneous transhepatic intubation and combined internal-external drainage of the biliary system was performed in 15 patients with occlusion of the extrahepatic bile ducts due mainly to cholangiocarcinoma, metastases of the hepatoduodenal ligament, and tumors of the periampullary region. The technique is described and the value of the procedure in temporary decompression and combined internal-external bile drainage prior to radical surgery is demonstrated. Its advantages as a palliative method are evident in far-advanced malignancy when extensive and complicated surgical procedures are ill-advised.

Adult↗
PubMed1979

Carcinoma arising in the wall of congenital bile duct cysts.

The incidence of carcinoma arising in the wall of the congenital bile duct cysts is much higher than previously assumed. The authors report 4 such cases of primary and secondary carcinomas and review their clinical features through the similar 59 cases in the literature. Of the 63 cases, the average age was much younger, at least several decades, compared with cases of extra-hepatic carcinoma without bile duct cysts. The female-male ratio was 2.5:1. Racial preponderance was also observed, namely, the majority were Japanese. Additionally, many patients previously received various internal drainage procedures, especially choledochocystoduodenostomy. As the treatment, primary excision of the extrahepatic bile duct cyst seems to give the best results because it can avoid ascending cholangitis and prevent development of carcinoma. However, carcinoma still can arise in the intrahepatic bile duct cyst, which cannot be removed at the present time.

Adenocarcinoma↗
PubMed1979

[Computerized tomography in the evaluation (author's transl)].

CT can clearly demonstrate dilation of intra- and extra-hepatic bile ducts due to mechanical obstruction. Note is made that the intrahepatic bile must not necessarily participate in dilation in obstructive jaundice. The cause in 27 cases observed in our institutions was as follows: 16 pancreatic tumors; 1 stone; 2 extrahepatic bile duct obstructions; 4 liver lesions (tumor and cirrhosis) and 4 with cause unknown. Furthermore, CT is helpful in the evaluation of hepatogenic non-obstructive jaundice such as due to primary liver cell carcinoma (hepatoma), metastases to the liver and advanced cirrhosis of the liver. The value of CT in the evaluation of different types of cholestasis is demonstrated by several exemplary cases; and the problems of differential diagnosis are pointed out.

Adenocarcinoma↗
PubMed1977

Clinical aspects of intrahepatic bile duct carcinoma including hilar carcinoma: a study of 57 autopsy-proven cases.

The clinical features of 57 autopsied cases of intrahepatic bile duct carcinoma including 28 cases of the peripheral type (cholangiocarcinoma in the narrow sense) and 29 cases of the hilar type are described in comparison with those of hepatocellular carcinoma, with a review of the literature on the clinicopathological aspects of intrahepatic bile duct carcinoma. As compared with hepatocellular carcinoma, the average age of the patients was older; the male predominance was not obvious, chronic parenchymal liver disease was infrequent in the past history, association of primary cirrhosis was seldom, cholestatic features were frequently the early signs and more pronounced during the course, the liver was enlarged to a lesser extent, ascites was less common, signs of portal hypertension were absent or minimal, and extrahepatic metastases were less frequent. In many respects, the hilar type resembled extrahepatic bile duct carcinoma, and the peripheral type was somewhat between it and hepatocellular carcinoma. Although the overall survival was not much different from that for hepatocellular carcinoma, early diagnosis is emphasized; this would make surgical management possible. Differential diagnosis from hepatocellular carcinoma may be possible in the majority with direct cholangiography, liver scan, celiac angiography, determination of alpha-fetoprotein and hepatitis B antigen, and blood chemistry such as SGOT, SLDH, serum bilirubin and alkaline phosphatase. Illustrative cases are given including one patient with a hilar carcinoma who survived for more than 2 years after transhepatic biliary drainage.

Adenoma, Bile Duct↗