Endoscopic nasobiliary drainage tube placement through a periampullary perforation for management of intestinal leak and necrotizing pancreatitis.

Video 1Management of ampullary perforation by endoscopic nasobiliary drainage tube placement through the perforation for suctioning out leaked intestinal juice and indicating the presence of the hepatic portal vein.

Evaluation of the Cell Block Method Using Overnight-Stored Bile for Malignant Biliary Stricture Diagnosis.

The specimen collection and subsequent pathological diagnosis of malignant biliary stricture (MBS) are difficult. This study aimed to determine whether the cell block (CB) method using overnight-stored bile is useful in the diagnosis of MBS. This trial was a single-arm prospective study involving a total of 59 patients with suspected MBS. The primary endpoint was cancer detectability and accuracy using the CB method, and a comparison with the detectability and accuracy achieved with bile cytology was made. The immunohistochemical sensitivity for maspin and p53 was also investigated in the CB and surgical specimens. We were able to collect bile from all 59 patients, and 45 of these patients were clinically diagnosed with MBS. The cancer detectability using the CB method (62.2%) was significantly higher than that using cytology (37.8%) (p = 0.0344). When CB was combined with biopsy, the rates of cancer detectability (75.6%) and accuracy (81.4%) increased. In eight patients who received surgical therapy, maspin- and p53-immunohistochemistry was applied to the surgical and CB specimens, and cancer cells in both specimens showed positive cytoplasmic and nuclear staining for maspin and nuclear staining for p53. The CB method is, thus, useful for detecting malignancy (UMIN000034707).

Granulocyte colony-stimulating factor impairs liver regeneration in mice through the up-regulation of interleukin-1beta.

BACKGROUND/AIMS: Stem cell induction via granulocyte colony-stimulating factor (G-CSF) administration is utilized in the treatment of various diseases. Therefore, we examined the effect of G-CSF administration to a liver fibrosis model induced by dimethylnitrosamine (DMN). METHODS: ICR mice were subcutaneously injected with either G-CSF (150microg/kg) or saline at days 0, 3, 7 and 10. Subacute liver injury was established by intraperitoneal injection of DMN (10mg/kg) on three consecutive days of each week. RESULTS: G-CSF administration significantly decreased the survival rate of mice treated with DMN. There was no difference in the degree of liver injury or fibrosis between either group of mice. However, assessment by proliferating cell nuclear antigen (PCNA) revealed that the G-CSF-treated mice experienced a greater degree of inhibition of liver cell proliferation than the control mice. Interleukin-1beta (IL-1beta) mRNA expression increased in the livers of G-CSF-treated mice. PCNA staining and analysis of cell cycle-related proteins also revealed that passive immunization with anti-IL-1beta-neutralizing antibody improved the impaired hepatocellular regeneration and resulted in an improved survival rate of mice treated with G-CSF and DMN. CONCLUSIONS: G-CSF administration suppressed liver cell proliferation through the up-regulation of IL-1beta expression in DMN-induced liver injury.

Actin organization and hepatocyte differentiation are regulated by extracellular matrix via PI-4,5-bisphosphate in the rat.

Cell adhesion to the extracellular matrix (ECM) plays vital roles in both morphogenesis and regulation of gene expression in cells of adult organisms. How intracellular, cytoskeletal, and signaling factors connect and communicate with the ECM is a fundamental question. Using a cDNA microarray analysis, we identified phosphatidylinositol 4,5-bisphosphate (PI[4,5]P2) phosphatase mRNA as being up-regulated in hepatocytes cultured on a basement membrane matrix, Engelbreth-Holm-Swarm (EHS) gel, which led to the finding that the PI(4,5)P2 levels of hepatocytes decreased on EHS gel. These changes in hepatocytes on EHS gel were accompanied by promotion of actin depolymerization and differentiated phenotypes of the hepatocytes. Treatment with PI(4,5)P2 or a phospholipase C inhibitor, U73122, resulted in decreased mRNA expressions of albumin and hepatocyte nuclear factor 4 (HNF-4) in hepatocytes. In contrast, actin-disrupting agent gelsolin increased mRNA expressions of albumin and HNF-4. In conclusion, organization of the actin cytoskeleton via PI(4,5)P2 is involved in the regulation of hepatocyte differentiation by the ECM.

Hepatocyte nuclear factor-4alpha and -1 small interfering RNA inhibits hepatocyte differentiation induced by extracellular matrix.

Liver-specific genes and hepatocyte nuclear factor (HNF)-4alpha and -1 are coordinately regulated by extracellular matrix (ECM). However, still are unclear interactions between liver-specific genes and these liver-enriched transcription factors in the mechanism of hepatocyte differentiation regulated by ECM. To elucidate the relationship, we used small interfering RNA (siRNA), which obtains strong and specific knockdown of gene expression in cell culture. Treatment with siHNF-4alpha and siHNF-1 declined the expression levels for HNF-4alpha mRNA and HNF-1 mRNA in primary rat hepatocytes, respectively. The mRNA expressions of albumin, transthyretin, and apolipoproteins that were up-regulated in hepatocytes cultured on a basement membrane matrix, Engelbreth-Holm-Swarm (EHS) gel, were decreased in the presence of siHNF-4alpha or siHNF-1. Moreover, siHNF-4alpha and siHNF-1 did not affect the morphology and actin assembly of hepatocytes. These findings demonstrated that HNF-4alpha and HNF-1 directly regulate liver-specific gene expression and might be downstream of cytoskeletal organization in the mechanism by which the differentiated phenotype of hepatocytes is regulated by EHS gel.