Hepatic Bud Research Articles

Infarcted accessory liver lobe in a pediatric patient: A case report

Accessory liver lobe (ALL) is a rare abnormality of the liver that occurs during the third week of pregnancy due to the division of the hepatic bud and distortion of the endodermal caudal foregut. ALLs are typically asymptomatic. However, they can become twisted and cause acute abdominal pain. There have been 24 reported cases of ALL torsion in children, most of which required urgent surgical removal. A seven-year-old boy presented to the emergency room with one day of abdominal pain in the epigastric and right hypochondrium areas. Upon physical examination, localized rigidity was observed in the upper hemiabdomen, CT scan revealed a mass originating from the liver. Based on the clinical examination and the CT findings a diagnosis of acute abdomen was made and the patient underwent an emergency laparotomy. During the operation, a mass was found to be connected to the liver through a twisted pedicle. The pedicle was transected, and the mass completely removed. The histopathology report confirmed that the mass was an infarcted ALL and ruled out thrombosis or a neoplasm. Postoperatively the patient developed a bile leak at the base of the transected ALL pedicle, which was managed with a Roux-en-Y hepaticojejunostomy. Making a definitive diagnosis of ALL before surgery may be difficult, even with advanced imaging. Pediatric surgeons should include ALL torsion in the differential diagnosis of acute abdominal pain in children when a mass adjacent to the liver is found on the preoperative images.

A Case Report on Hepatopancreatic Anomaly with its histomorphological study in Adult Cadaver

The pancreas is a soft, lobulated and mixed gland. As the liver and pancreas develop together from the hepatopancreatic bud it is common that congenital anomalies of liver and pancreas exist together. This study was done during routine practical dissection where a band of tissue was found extending from the head of the pancreas to the root of the Mesentry. On histological examination the tissue was confirmed to be pancreas. It is seen that the hepatic bud grows at the expense of the ventral pancreas. In the present study, we found an atrophied left lobe of liver and an abnormally rare and large uncinate process of pancreas. KEY WORDS: Uncinate Process, Pancreas, Hepatopancreatic Bud, Accessory Lobe.

A rare case of accessory liver lobe torsion in a pediatric patient who showed recurrent epigastralgia and who was treated by elective laparoscopic resection

BackgroundAccessory liver lobe (ALL) is a rare liver malformation. An ALL develops due to malformation of the endodermal caudal foregut and segmentation of the hepatic bud in the third week of gestation. Most ALLs are asymptomatic and are detected incidentally during abdominal surgery. The incidence of ALL is < 1% in patients who undergo abdominal surgery. However, some ALLs twist and cause acute abdomen. We experienced a pediatric case of ALL torsion in a patient who underwent elective laparoscopic surgery.Case presentationThe 5-year-old girl had a 3-month history of epigastralgia and vomiting, which occurred every 2 weeks. Abdominal ultrasonography with color Doppler imaging revealed an 11.8 × 13.6 mm nonvascular lesion with mixed echogenicity near the round ligament of the liver. Enhanced computed tomography confirmed a 14 × 16 × 20 mm low-attenuation mass surrounded by a hyperdense line and disproportionate fat stranding on the right side of the round ligament of the liver. There was no ascites or hemorrhage. These findings suggested an abscess of the round ligament of the liver. Her symptoms improved with the administration of oral antibiotics; thus, we planned to perform elective exploratory laparoscopy and subsequent resection. Two trocars (5 mm) were inserted through a multichannel port device at the umbilicus and one trocar (3 mm) was inserted at the right lateral abdomen. Upon observation of the abdominal cavity, the omentum was observed adhering to the round ligament of the liver. Macroscopic observation revealed no apparent mass lesions. We performed adhesiolysis of the omentum from the round ligament of the liver using a vessel sealing system. We performed resection at the site at which adhesion had formed between the round ligament of the liver with the surrounding tissue using a vessel sealing system and the resected specimen was extracted through the umbilical wound. The postoperative course was uneventful. A pathological examination revealed necrotic liver tissue. The resected tissue was founded to be an ALL with ischemic change.ConclusionsThe recurrent abdominal pain was induced by torsion of the ALL. Pediatric surgeons should consider ALL torsion as a differential diagnosis for epigastralgia of unknown etiology.

Progress of GATA6 in liver development.

GATA binding protein 6 (GATA6) is a member of the GATA family of zinc-finger transcriptional regulators, whose names come from the conservative base sequence (G/A)GATA(A/T). The GATA families play key roles in cell fate determination, proliferation, migration, and organogenesis of endoderm- and mesoderm-derived organs in vertebrates. As a lineage-specific factor, a chromatin remodeling factor, a pluripotent factor and a pioneer factor, GATA6 is involved in various stages of liver development, including endoderm liver-lineage determination, liver specification, hepatic bud outgrowth and hepatoblast differentiation. In this review, we summarize recent progress in the roles and regulatory mechanisms of GATA6 in liver development.

GATA4 loss in the septum transversum mesenchyme promotes liver fibrosis in mice

The zinc finger transcription factor GATA4 controls specification and differentiation of multiple cell types during embryonic development. In mouse embryonic liver, Gata4 is expressed in the endodermal hepatic bud and in the adjacent mesenchyme of the septum transversum. Previous studies have shown that Gata4 inactivation impairs liver formation. However, whether these defects are caused by loss of Gata4 in the hepatic endoderm or in the septum transversum mesenchyme remains to be determined. In this study, we have investigated the role of mesenchymal GATA4 activity in liver formation. We have conditionally inactivated Gata4 in the septum transversum mesenchyme and its derivatives by using Cre/loxP technology. We have generated a mouse transgenic Cre line, in which expression of Cre recombinase is controlled by a previously identified distal Gata4 enhancer. Conditional inactivation of Gata4 in hepatic mesenchymal cells led to embryonic lethality around mouse embryonic stage 13.5, likely as a consequence of fetal anemia. Gata4 knockout fetal livers exhibited reduced size, advanced fibrosis, accumulation of extracellular matrix components and hepatic stellate cell (HSC) activation. Haploinsufficiency of Gata4 accelerated CCl4 -induced liver fibrosis in adult mice. Moreover, Gata4 expression was dramatically reduced in advanced hepatic fibrosis and cirrhosis in humans. Our data demonstrate that mesenchymal GATA4 activity regulates HSC activation and inhibits the liver fibrogenic process.

Caracterização histológica do desenvolvimento hepático em diferentes estágios embrionários de ratos

Os ratos apresentam desenvolvimento embrionário similar aos de animais domésticos e humanos, sendo assim um modelo válido para estudos científicos. Dentre eles, o F344 se destaca por ser uma linhagem isogênica, facilitando a leitura dos resultados obtidos, devido a sua homogeneidade gênica. Devido à falta de estudos histológicos acerca do desenvolvimento hepático em ratos, o presente estudo tem como objetivo caracterizar histologicamente pela primeira vez o processo de desenvolvimento hepático nos estágios embrionários de E12,5 (12,5 dias de gestação), E13,5, E14,5, E15,5 e E16,5 em ratos F344. Cinco embriões de cada estágio embrionário foram coletados, fixados em Metacarn, incluídos em paraplast e realizadas colorações histológicas e histoquímica. Os brotos hepáticos de embriões entre 12,5-14,5 dias apresentaram-se como aglomerados de hepatoblastos, ainda desorganizados e circundados por inúmeras células precursoras sanguíneas nucleadas. Observou-se que os hepatoblastos possuem um núcleo grande basofílico com pouco citoplasma. Sinusoides com eritroblastos e células de Kupffer também foram encontrados. Com 14,5 dias, foi observada a coexistência de hepatoblastos e hepatócitos, além de megacariócitos. Nos embriões com 15,5 dias, começou a verificar-se distinção entre os cordões de hepatócitos em formação, limitados pelos capilares sinusoides. Tais cordões começavam a confluir para as presentes veias centrolobulares. Com 16,5 dias, a arquitetura parenquimal estava mais próxima da encontrada em fígados adultos, sendo a quantidade de hepatócitos superior à de hepatoblastos. Nesse prazo gestacional, o fígado ainda tinha função hematopoiética. O estudo traz histologicamente o desenvolvimento hepático entre 12,5-16,5 dias de ratos da linhagem F344, evidenciando as células que compõem cada período gestacional, gerando subsídios para futuros estudos.

Ciliated hepatic foregut cyst: two further cases with an immunohistochemical analysis.

The objective of the present study is to report two cases of a rare entity, which is being increasingly recognized in recent years. A 35-year-old woman and a 33-year old man were incidentally discovered to have bilocular cystic hepatic masses affecting segment IV. In both cases the cystic mass was excised and the histopathological analysis revealed an inner lining of the cyst wall with a pseudostratified epithelium showing prominent cilia. The cyst wall contained some muscular fibers but no cartilage or other tissue types and diagnosis was ciliated hepatic cyst. Both patients recovered uneventfully after surgery and are well and disease free. Ciliated hepatic cysts are rare cystic hepatic masses derived from remnants of the embryonal foregut that are embedded inside the hepatic bud during embryological development. Fewer than 100 cases of this tumor have been reported in the world literature, many of them in Japan, and most cases have behaved in a benign fashion, although there are at least three reported cases of malignancy within the cyst wall to a squamous cell carcinoma. We herein report two further cases of this entity, highlight the diagnostic usefulness of immunohistochemistry and comment on the possible therapeutic alternatives.

Hepatobiliary and Pancreatic: Agenesis of the gallbladder

Aman, aged 41, was seen in the Emergency Service because of the acute onset of pain in the right upper quadrant of the abdomen that was associated with nausea. He described similar episodes on two previous occasions. On examination of the abdomen, the only abnormality was mild tenderness on palpation over the right upper quadrant. Screening blood tests including liver function tests and serum amylase were within the reference range. His pain settled with analgesia and he was given an outpatient appointment for an upper abdominal ultrasound scan. The gallbladder was poorly seen but the possibility was raised of a contracted gallbladder with multiple stones. Because of continuing minor symptoms, he was advised to proceed with elective laparoscopic cholecystectomy.At operation, it was not possible to identify the gallbladder. The appearance of the gallbladder fossa is shown in Figure 1. Magnetic resonance cholangiopancreatography (MRCP) was performed after surgery and showed congenital absence of the cystic duct and gallbladder (Figure 2). An incidental finding was that of pancreas divisum. Agenesis of the gallbladder is a rare congenital anomaly with an estimated prevalence of between 1 and 10 per 10,000 people in the general population. The anomaly is usually sporadic although there are occasional reports of two affected members within families. Embryologically, the anomaly is presumed to arise because of a defect in the development of the gallbladder bud that arises from the caudal portion of the hepatic bud. Most patients do not have a cystic duct stump. At surgery, gallbladder agenesis should only be diagnosed after a careful search of ectopic locations, particularly an intrahepatic or left-sided gallbladder. Intraoperative cholangiography may also be helpful if the bile duct can be readily identified. However, extensive surgical dissection of the area should be avoided as this may result in injury to hilar structures. MRCP either before or after surgery may also be helpful in those patients with uncertain results from ultrasound or computed tomography scans. In the above patient, possible causes for pain include an atypical irritable bowel syndrome, a motility disorder of the sphincter of Oddi and perhaps pancreas divisum. There are also rare reports of agenesis of the gallbladder with primary bile duct stones.

Fibroblast Growth Factor Receptor 2 Expression Is Associated with Hepatic Progenitor Cell Expansion in the DDC Model

Introduction: Liver transplantation, the only curative treatment for end-stage liver failure, is limited by the availability of donor organs; therefore, other potential methods of hepatocyte replacement, such as hepatic progenitor cell (HPC) transplantation, require investigation. Fibroblast Growth Factors (FGFs) are required for induction of the hepatic bud from the foregut endoderm at the initial stages of hepatogenesis. We recently showed that FGF10 promotes HPC survival and proliferation via β-catenin activation through receptor FGFR2IIIb activation.

Crucial role of vHNF1 in vertebrate hepatic specification

Mouse liver induction occurs via the acquisition of ventral endoderm competence to respond to inductive signals from adjacent mesoderm, followed by hepatic specification. Little is known about the regulatory circuit involved in these processes. Through the analysis of vHnf1 (Hnf1b)-deficient embryos, generated by tetraploid embryo complementation, we demonstrate that lack of vHNF1 leads to defective hepatic bud formation and abnormal gut regionalization. Thickening of the ventral hepatic endoderm and expression of known hepatic genes do not occur. At earlier stages, hepatic specification of vHnf1-/- ventral endoderm is disrupted. More importantly, mutant ventral endoderm cultured in vitro loses its responsiveness to inductive FGF signals and fails to induce the hepatic-specification genes albumin and transthyretin. Analysis of liver induction in zebrafish indicates a conserved role of vHNF1 in vertebrates. Our results reveal the crucial role of vHNF1 at the earliest steps of liver induction: the acquisition of endoderm competence and the hepatic specification.

The Onecut transcription factors HNF-6/OC-1 and OC-2 regulate early liver expansion by controlling hepatoblast migration

Liver development in mammals is initiated by the formation of a hepatic bud from the ventral foregut endoderm. The hepatic cells then proliferate and invade the septum transversum mesenchyme, and further differentiate to give rise to hepatocytes and biliary cells. By analyzing mice that are knockout for the transcription factors Hepatocyte Nuclear Factor-6 (HNF-6)/Onecut-1 (OC-1) and OC-2, we show here that these factors redundantly stimulate the degradation of the basal lamina surrounding the liver bud and promote hepatoblast migration in the septum transversum. Gene expression analysis indicates that HNF-6 and OC-2 belong to a gene network comprising E-cadherin, thrombospondin-4 and osteopontin, which regulates liver bud expansion by controlling hepatoblast migration and adhesion. This network operating at the onset of liver development contains candidate genes for investigation of liver carcinogenesis.

Mutations affecting liver development and function in Medaka, Oryzias latipes, screened by multiple criteria

We report here mutations affecting various aspects of liver development and function identified by multiple assays in a systematic mutagenesis screen in Medaka. The 22 identified recessive mutations assigned to 19 complementation groups fell into five phenotypic groups. Group 1, showing defective liver morphogenesis, comprises mutations in four genes, which may be involved in the regulation of growth or patterning of the gut endoderm. Group 2 comprises mutations in three genes that affect the laterality of the liver; in kendama mutants of this group, the laterality of the heart and liver is uncoupled and randomized. Group 3 includes mutations in three genes altering bile color, indicative of defects in hemoglobin–bilirubin metabolism and globin synthesis. Group 4 consists of mutations in three genes, characterized by a decrease in the accumulation of fluorescent metabolite of a phospholipase A 2 substrate, PED6, in the gall bladder. Lipid metabolism or the transport of lipid metabolites may be affected by these mutations. Mutations in Groups 3 and 4 may provide animal models for relevant human diseases. Group 5 mutations in six genes affect the formation of endoderm, endodermal rods and hepatic bud from which the liver develops. These Medaka mutations, identified by morphological and metabolite marker screens, should provide clues to understanding molecular mechanisms underlying formation of a functional liver.

Fibroblast growth factors promote hepatocyte stem cell renewal in embryonic liver cultures

Fibroblast growth factors (FGFs) have been shown to play a definite role in hepatic induction. Stage and tissue specific expression of FGF 1,4 and 8 are necessary for initiation of hepatic bud from the foregut endoderm FGF is also routinely used to maintain and propagate embryonic stem ceils in culture. The aim of this study was to investigate the effect of FGF 1, 4 and 8 on liver development utilizing an in vitro embryonic liver culture system and recotnbinant FGF proteins. Livers were harvested from day 10 embryos (El0) and cultured as an organ in DMEM supplemented with 10% FCS (control) with or without additional FGF 1 or FGF 4 or FGF 8. After 72 hours, the cultured livers were fixed and processed and 4/zm sections were utilized for histologic and immunohistochemical evaluation. Proliferation (PCNA and Ki-67) and apoptosis (TUNEL) assay was also performed. The major difference in the histology of the FGF 1/4/8 treated cultures was in the arrangement of cells in sheet like architecture only as compared to the controls that displayed cells in both ductular and sheet like arrangements. There was no significant change in number of apoptotic cells in presence of FGF 1/4 but there was a decrease in number of apoptotic nuclei in FGF8 treated cultures. Almost all cells in all FGF cultures exhibited PCNA positivity and a sigmficant number of cells were Ki-67 (S-phase) positive. There was a striking difference in the number of c-kn positive stem cells in the presence of any of the three FGFs used as compared to the controls. These stem cells were also positive for a-fetoprotein and albumin and very few were positive for CK-19. There was an overall decrease in number of CK-19 positive cells in presence of the FGFs. To conclude, FGF 1, 4 and 8 are excellent growth factors to maintain and propagate liver stem cells in development. These factors support prohferation and affect apoptosis and thus promote liver stem cell renewal. Also, lineage analysis shows a preponderance of unipotential stem cells (more hepatocytic than biliary) in the FGF treated cultures that suggest existence of selective hepatocyte stem ceils, h appears that FGFs promotes self-renewal of such a unipotential stem cell population in the liver.

RanGTPase expression during early development of the mouse embryo

Ran is a small GTP-binding protein involved in several essential roles for cell viability. This observation implies Ran might be ubiquitously expressed during development. However, Ran shows a differentiated expression pattern that is restricted to specific tissues from embryo to adult. At early embryonic stages of mouse development we found persistent Ran expression in proliferating neural tissue, neural crest derived dorsal root ganglions and sensory pits. We also showed an accumulation of Ran transcripts in main embryonic haematopoietic tissues: blood islands first and then hepatic bud. In advanced stages of development Ran is also expressed in other tissues showing a high cell turnover.

Coexpression of the C-MYC protooncogene with α-fetoprotein and albumin in fetal mouse liver

Abstract The level of mRNAs for the c-myc protooncogene and the serum proteins α-fetoprotein (AFP) and albumin in liver, visceral yolk sac and gut between day 9 and day 19 of mouse gestation was studied by in situ hybridization employing single-stranded RNA probes. In the prehepatocyte population, c-myc was coexpressed with albumin and AFP. No heterogeneity was noted within this cell population with respect to the expression of these mRNAs up to day 15. AFP expression was high in the liver primordium and rose further until day 15. Albumin mRNA was expressed weakly but distinctly in the hepatic bud and increased throughout fetal life. C-myc expression in prehepatocytes exhibited a maximum around day 13 and a dramatic decline after day 15, but was much lower in other cell types of the fetal liver. In the visceral yolk sac, AFP was strongly expressed, with albumin expression first becoming detectable at day 13, while c-myc mRNA was detected up to day 9. In the endodermal gut epithelium, c-myc expression was high, albumin mRNA was not detected and AFP message was restricted to individual loops of the gut. These results suggest that a period of high c-myc expression in the developing liver may allow rapid expansion of the prehepatocyte population at a specific stage of differentiation.

Foetal haemopoiesis during the hepatic period. I. Relation between in vitro liver organogenesis and erythropoietic function.

Cultures of the hepatic bud, under different experimental conditions, show a direct relation between foetal age at the time of dissection and the further organogenesis of the explant. In cultures of the septum transversum plus hepatic bud--with or without splanchnic mesenchyme--obtained from embryos of four to 25 somites, the capacity for endodermic cells to differentiate into hepatocytes appears only in a small number of samples; whereas, in the hepatic bud from older embryos (26 to 40 somites), this differentiation occurs in all cases. The amount of time cultures were allowed to grow was important for hepatic organogenesis, as measured by cord-like organization of hepatocytes plus their storage capacity of glycogen. The possibility of the explants showing complete haemopoiesis was also a condition of foetal age at the time of explant. Haemopoiesis was not found in cultures from embryos of less than 25 somites. On the other hand, development of haemopoiesis did not show a direct relation to days of culture, since the peak of this activity was observed towards the third day in vitro. Most explants showed a generalized haemopoiesis (both interstitial and vascular) with a decay towards the sixth day. Endodermal cells of the hepatic bud were capable of both proliferation and differentiation into hepatocytes, even in those mesenchymes considered inadequate such as limb mesenchyme. In the latter case we were unable to find haemopoiesis at any time. The septum transversum, when cultured alone, did not contain haemopoietic cells.

Mise en évidence de glycogène et d’une activité de la glycogène synthétase dans l’ébauche hépatique aux stades précoces du développement embryonnaire chez le poulet

ABSTRACT Detection of glycogen and glycogen synthetase activity in the hepatic primordium of chick embryo at early developmental stages Glycogen has been detected cytochemically in the chick hepatic primordium at early developmental stages. The cytochemical methods used are PAS according to Hotchkiss &amp; MacManus after fixation by Gendre’s fluid at —20 °C and rapid dehydration at 4 °C and Thiery’s technique for polysaccharide detection at the electron microscopic level. Previous authors reported that glycogen appears in the hepatocytes during the sixth or seventh day of incubation in the chick embryo. In fact, the more sensitive methods used here show that this substance is present in the determined presumptive hepatic endoderm as early as the 20-somite stage, some hours before the formation of the primary hepatic bud. Glycogen is present in an approximately constant amount in the differentiating hepatic endoderm as β particles (according to Drochmans’ nomenclature) from the 20-somite stage to the sixth day of incubation. Then the hepatocyte glycogen content increases rapidly as had previously been shown by biochemical methods and a rosettes appear in the cell. A glycogen synthetase activity has been detected at the end of the fourth day of incubation (96 h). This activity increases sharply from the sixth day of incubation to reach a maximal value at .12 days and then decreases until hatching. The possible regulatory mechanisms of glycogen synthesis in differentiating liver cells of avian embryos are discussed.