β-Adrenoceptor blockade in sclerosing cholangitis of Mdr2 knockout mice: antifibrotic effects in a model of nonsinusoidal fibrosis.

Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with high propensity to develop into cholangiocarcinoma. The hepatobiliary disorder of PSC is due to progressive fibrosis surrounding the intra- and extrahepatic bile ducts. Until now, no effective medical therapy exists.

Neighbor of Punc E11, a novel oncofetal marker for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the 5th common malignancy worldwide, but established markers fail to detect up to one third of HCC. We have recently identified Neighbor of Punc E11 (Nope) as a surface marker for murine fetal liver stem cells. Similar to commonly used HCC markers such as α-Fetoprotein (Afp) and Glypican-3 (Gpc-3), we here establish Nope as an oncofetal marker of murine and human HCC and investigate its specific expression in hepatoma cell lines and primary HCC.

Tissues from routine pathology archives are suitable for microRNA analyses by quantitative PCR.

Background: MicroRNAs have recently taken centre stage as short non-coding RNAs that regulate mRNA expression.

Aim/methods: To assess the feasibility of using microRNA techniques on routinely processed tissues, the accessibility of two representative microRNAs was examined by real-time quantitative PCR in 86 human formalin-fixed paraffin-embedded (FFPE) samples from liver, breast, bone marrow, lymphatic tissues and colon. Murine liver was used to analyse the influence of fixation time and different fixatives.

The role of microRNAs in primary liver cancer.

Small RNA molecules such as microRNAs, for many years considered to be superfluous genomic material, are now known to play important regulatory roles in apoptosis, cell proliferation and differentiation, angiogenesis and thus in carcinogenesis. Primary liver carcinomas such as hepatocellular carcinomas, cholangiocarcinomas and mixed variants show a rising incidence with high mortality among affected patients but lack effective targeted therapies except the new multiple kinase inhibitor Sorafenib. This review elucidates the recent contributions of miRNA gene expression analyses to a better understanding of the complex molecular interactions in liver carcinogenesis and highlights their future promise to provide novel tools for improved diagnostics, more accurate prognostic assessment and tailored molecular therapies in liver cancer.

MicroRNA gene expression profile of hepatitis C virus-associated hepatocellular carcinoma.

Unlabelled: MicroRNAs are small noncoding RNAs that regulate gene expression by targeting messenger RNAs (mRNAs) through translational repression or RNA degradation. Many fundamental biological processes are modulated by microRNAs, and an important role for microRNAs in carcinogenesis is emerging. Because understanding the pathogenesis of viral-associated hepatocellular carcinomas is important in developing effective means of classification, prognosis, and therapy, we examined the microRNA expression profiles in a large set of 52 human primary liver tumors consisting of premalignant dysplastic liver nodules and hepatocellular carcinomas by quantitative real-time polymerase chain reaction.

Giant polypoid gastric heterotopia of the jejunum presenting with intermittent intussusception.

We report the case of a 17-year-old female with symptoms of intermittent small bowel obstruction. Computed tomography scan of the abdomen revealed an intussusception. The patient underwent a laparoscopic-assisted resection of the mass, which proved to be gastric heterotopia of the jejunum.

Fallopian tube prolapse mimicking aggressive angiomyxoma.

A 68-year-old woman presented with a 4-cm polypoid bleeding mass protruding from the vaginal apex 30 years after vaginal hysterectomy. Laparotomy did not confirm the clinical suspicion of bowel prolapse and led to resection of the mass. Microscopic examination revealed a hypocellular edematous lesion with glandular areas resembling fallopian tube epithelium.

Glucagon-like peptide 2 is an endogenous mediator of postresection intestinal adaptation.

Background: After massive small bowel resection, the remnant intestine undergoes compensatory adaptation. We tested the hypothesis that glucagon-like peptide-2 (GLP-2) is an endogenous mediator of postresection intestinal adaptation.

Methods: Rats were allocated to 1 of 4 groups: groups 1 and 2 rats underwent mid-small bowel transection and reanastomosis; groups 3 and 4 rats underwent 75% mid-small bowel resection and reanastomosis.

Pulmonary capillary hemangiomatosis arising in hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is an autosomal dominant inherited disease characterized by epistaxis, telangiectases, and visceral arteriovenous malformations that can lead to hemorrhage and other complications. We report the case of a 56-year-old female patient with HHT and pulmonary hypertension who died with intractable pulmonary and gastrointestinal bleeding. Autopsy revealed vascular malformations in the lungs, gastrointestinal tract, liver, spleen, and brain.

Biliary adenofibroma: a rare neoplasm of bile duct origin with an indolent behavior.

We report a case of biliary adenofibroma in a 47-year-old woman, who presented with right upper quadrant pain for several months. Abdominal imaging revealed a 16-cm solid and cystic mass in the left hepatic lobe. Histologically, the tumor showed two distinct components: 1) cystic and tubular structures lined by low columnar to cuboidal biliary-type epithelium, and 2) a dense fibrous stroma composed of spindle-shaped cells with only mild nuclear pleomorphism and inconspicuous nucleoli.

Gene expression profiles of human breast cancer progression.

Although distinct pathological stages of breast cancer have been described, the molecular differences among these stages are largely unknown. Here, through the combined use of laser capture microdissection and DNA microarrays, we have generated in situ gene expression profiles of the premalignant, preinvasive, and invasive stages of human breast cancer. Our data reveal extensive similarities at the transcriptome level among the distinct stages of progression and suggest that gene expression alterations conferring the potential for invasive growth are already present in the preinvasive stages.

C-met and hepatocyte growth factor expression in combined hepatocellular and cholangiocarcinoma.

The membranous tyrosine kinase receptor c-met and its natural ligand hepatocyte growth factor are prominent mitogens, motogens and morphogens for hepatocytes and many other cell types in vitro as well as in vivo. To clarify the significance of the c-met/hepatocyte growth factor system in the development and spread of combined hepatocellular and cholangiocarcinoma, surgical specimen from 30 patients, consisting of 4 double cancers, 20 combined types and 6 mixed types, were examined immunohistochemically. Immunoreactivity for HGF was significantly correlated with the differentiation degree of cholangiocellular components, being highest in well and moderately differentiated and lowest in poorly differentiated components (p=0.

Retrospective analysis of prognostic factors after liver resection and transplantation for cholangiocellular carcinoma.

Background: Cholangiocellular carcinoma is an uncommon primary liver cancer, which may be mixed with hepatocellular carcinoma. A retrospective analysis was undertaken to evaluate the results of surgical treatment and to identify prognostic factors.

Methods: Between 1978 and 1996, 162 patients underwent surgery for cholangiocellular carcinoma: liver resection (n = 95), liver transplantation (n = 24) and exploratory laparotomy with and without drainage (n = 43).