Development of extrahepatic bile duct excluding gall bladder in human fetuses: histological, histochemical, and immunohistochemical analysis.

BACKGROUND: The fetal development of extrahepatic bile ducts (EBD) is unkown. MATERIALS AND METHODS: Development of EBD was examined by immunohistochemistry in 16 fetuses of 7-40 gestational week (GW). Gall bladder (GB) was not investigated. RESULTS: At seven GW, a hepato-pancreatic bud (HPB) was seen near the hepatic hilus. At eight GW, embryonic EBD, GB and pacreas developed from HPB. Portal veins (PV) and hepatic arteries (HAs) were present in EBD at eight GW. Liver parenchyma was already present in seven GW. At eight GW, EBD at porta hepatis (PH) was already established; PH EBD was derived from ductal plate (DP). The distal and middle EBD gradually develeped and took shape of EBD at nine GW. In PH, cystic and hepatic ducts developed from DP at eight GW. EBD developed further, accompanying many nerve fibers (NF) at PH and distal and middle EBD. Apparent PV and HA were seen around 12 GW. Around 20 GW, HA and capillaries proliferated, giving rise to peribiliary capillary plexus (PCP) in all parts of EBD. EBD grew gradually further, and around 30 GW extrahepatic peribiliary glands (EPG) emerged from EBD but not from cystic duct. Around 36 GW, exocrine pancreatic acinar cells emerged from remodeled DP at PH. At term (40 GW), EBD was established but was as yet immature. Numerous NF were present around EBD. Histochemically, EBD epithelium had no mucins at 7-12 GW but contained neutral and acidic mucins at 23-40 GW. EPG had abundant neutral and acidic mucins. Immunohistochemically, alpha-fetoprotein (AFP) was consistently positive in the epithelial and mesenychyma. The NF and muscles of HPB present at seven GW were positive for neural cell adhesion molecule (NCAM), neuron-specific enolase (NSE), platelet-derived growth factor receptor-α (PDGFRA), and KIT, but they disappeared in nine GW. Expressions of cytokeratin (CK) seven and CK19 in EBD and EPG were slight or none, while expression of CK8 was moderate, and that of CK18 was strong. NF were positive for NCAM, NSE, synaptophysin, and chromogranin, and PDGFRA. MUC1 and MUC6 apomucins were noted in EBD and EPG. EPG contained numerous endocrine cells positive for chromogranin, synaptophysin, NCAM and NSE. A few endocrine cells positive for these antigens were seen in EBD. Numeous KIT-positive stem cells (SC) were seen in PH, EBD, PV, HA, PCP, and EPG. NCAM-positive and bcl-2-positive SC were also located in these structures. Epithelial cells of EBD and EPG showed expressions of MET, PDGFRA, CA19-9, MUC1, MUC2, MUC6, KIT, bcl-2, and ErbB2. No expressions of HepPar1, carcinoembryonic antigen (CEA), and epithelial membrane antigen (EMA) were noted. CONCLUSIONS: Although the findings have limitatios because this study of humans are descriptive one, the present data suggest that the processes of the development and differentiation of EBD system may be associated with EBD SC, CK prolifes, SFC/KIT signaling, HGF/MET signaling, PDGRa/PDGFRA signaling, fibroblast growth factor/ErbB2 signaling, neuroendocrine lineage, NF differentiation, pancreatic aninar cell differentiation, PCP differentiation, MUC apomucins differentiation, and expressions of AFP and CA19-9. HepPar1, EMA and CEA were not involved in them.

Abnormalities of the gallbladder, clinical effects.

The aim of this review of the literature was to present and discuss the anatomical and embryological basis of congenital abnormalities of the gallbladder, based on a case of volvulus. In the rare cases of ectopic gallbladder, diagnosis of a biliary disease could be difficult. In such cases surgery can also be dangerous, especially when it is associated with abnormalities of the intra-hepatic biliary and vascular tree. This study, based on the embryology of the extra hepatic bile duct, focused on the most frequent gallbladder abnormalities to keep them in mind.

Liver development in the rat during the embryonic period (Carnegie stages 15-23).

Hepatic and biliary structures appearing during embryonic Carnegie stages 15-23 were analyzed in OFA rat embryos. The group of rats with crown rump length 7.5-16 mm and 12.8-16 days after coitus yielded 55 specimens (23 of stages 15-16, 20 of stages 17-18, 9 of stages 19-22 and 3 of stage 23). The embryos were submitted to serial histological sections with graphic reconstructions. From stage 15 to the end of the embryonic period, the hepatic gland and its vascular channels (transverse portal sinus and hepatocardiac veins) presented considerable enlargement while hematopoietic function appeared. At stage 17, occlusion due to epithelial proliferation was evident in the hepatic duct. At stage 18, the duct became recanalized and assured the continuity between liver cells and gut. From stage 18 to 23, biliary ductules developed in periportal connective tissue forming ductal plates which received biliary caniculi. Except for the gall-bladder which is never present in the rat, similarity and presence of the same hepatic structures in man and in the rat during the embryonic period stages 15-23 suggest that the rat is a good experimental model for liver development and will be useful in the understanding of congenital anomalies.

Human fetal development of the hepato-pancreatic duct junction--a possible explanation of congenital dilatation of the biliary tract.

Review of 20 cases of congenital dilatation of the common bile duct in childhood showed an association with anomalous choledocho-pancreatic junction in 8. Study of human fetuses showed that the choledocho-pancreatic junction was outside the wall of the duodenum before 8 wk gestation and moved inward and towards the duodenal lumen as age advanced. Arrest of this migration can explain the formation of the anomalous junction. Normal formation of the sphincter of Oddi may also be affected by this process, and lead to functional obstruction and dilatation of the common bile duct.

[A study of the early stages of biliary extrahepatic ducts organogenesis in the rat (Rattus norvegicus albinos) (author's transl)]. / De l'organogenèse des voies biliaires extrahépatiques chez le rat (Rattus norvegicus albinos). Contribution à l'étude des premiers stades.

In the early stages of morphogenesis, the hepatic diverticulum of the rat develops as in other mammals. Its anterior part gives rise to epithelial cell-cords bound by an epithelial primary plate to a single hepatic duct which joins the liver to the midgut. The interlobular bile-ducts develop from secondary epithelial plates which derivate from the primary one. The posterior part of diverticulum gives rise to a duct which may be assimilated by its position, structure and evolution, to the initial cystic duct of other mammals. This duct never participates to the formation of biliary extrahepatic ducts, but builds the ventral pancreas. Cellular necrosis is observed in relation with the development of the anterior part of diverticulum during the three first days of the hepatic morphogenesis.

Congenital hepatic duct obstruction with perforate diaphragms.

A patient had obstruction of the right and left hepatic ducts secondary to perforate diaphragms at the junction with the common hepatic duct. Transhepatic cholangiograms of both the right and left lobes were required to define the presence of diaphragms at the junctions of right, left, and common hepatic ducts. Excision of the diaphragms relieved the obstruction. A distinction should be made between congenital nonobstructive and congenital obstructive cystic dilation of intrahepatic biliary radicals.

[Development of the neural and tissue components of the excretory ducts of the liver, pancreas and Odd's sphincter in human embryogeny]. / Razvitie nervnykh i tkanevykh komponentov vyvodnykh protokov pecheni, podzheludochnoi zhelezy i sfinktera Oddi v émbriogeneze

The development of pancreatic, hepatic, cystic, common bile ducts, the Oddi's sphincter and their nervous apparatus were studied during prenatal human ontogenesis of fetuses and newborns. The process of formation of the nervous apparatus corresponds to the development of tissue structures of the ducts and the sphincter. The distinctions in the organization of nervous elements which are noted in adult humans are laid in the process of embryogenesis. These distinctions are especially pronounced in the structure of nervous plexuses and receptory endings. The nervous apparatus of the Oddi's sphincter region has a complex arrangement. This is the site of concentration of nerve nodules and receptory endings as well as abundant nervous connections between plexuses of the pancreatic head, duodenum and orifice zones of the both ducts. The receptors in nerve nodules and pericellular apparatuses on the bodies of ganglionic neurons were revealed.