Although the incidence of pancreatitis was higher, the overall stone clearance rate and risk of bleeding was lower with EPBD compared to EST.

Background and Aims Endoplasmic reticulum (ER) stress is associated with liver inflammation and hepatocellular carcinoma (HCC). However, how ER stress links inflammation and HCC remains obscure. Mesencephalic astrocyte‐derived neurotrophic factor (MANF) is an ER stress‐inducible secretion protein that inhibits inflammation by interacting with the key subunit of nuclear factor kappa light chain enhancer of activated B cells (NF‐κB) p65. We hypothesized that MANF may play a key role in linking ER stress and inflammation in HCC. Approach and Results Here, we found that MANF mRNA and protein levels were lower in HCC tissues versus adjacent noncancer tissues. Patients with high levels of MANF had better relapse‐free survival and overall survival rates than those with low levels. MANF levels were also associated with the status of liver cirrhosis, advanced tumor‐node‐metastasis (TNM) stage, and tumor size. In vitro experiments revealed that MANF suppressed the migration and invasion of hepatoma cells. Hepatocyte‐specific deletion of MANF accelerated N‐nitrosodiethylamine (DEN)‐induced HCC by up‐regulating Snail1+2 levels and promoting epithelial‐mesenchymal transition (EMT). MANF appeared in the nuclei and was colocalized with p65 in HCC tissues and in tumor necrosis factor alpha (TNF‐α)‐treated hepatoma cells. The interaction of p65 and MANF was also confirmed by coimmunoprecipitation experiments. Consistently, knockdown of MANF up‐regulated NF‐κB downstream target genes TNF‐α, interleukin (IL)‐6 and IL‐1α expression in vitro and in vivo. Finally, small ubiquitin‐related modifier 1 (SUMO1) promoted MANF nuclear translocation and enhanced the interaction of MANF and p65. Mutation of p65 motifs for SUMOylation abolished the interaction of p65 and MANF. Conclusions MANF plays an important role in linking ER stress and liver inflammation by inhibiting the NF‐κB/Snail signal pathway in EMT and HCC progression. Therefore, MANF may be a cancer suppressor and a potential therapeutic target for HCC.

Chemokines play a paramount role in tumor progression. In hepatocellular carcinoma (HCC) progression, chemokines and their receptors play an intricate role. Currently, chemokines and their receptors such as the CXCL12-CXCR4 axis, CX3CL1-CX3CR1 axis and the CCL20-CCR6 axis have received much research attention. Although a large number of studies show that these axes are strongly associated with HCC, the exact mechanism by which these axes promote the growth and progression of HCC remains unknown. In this paper, several chemokines and their receptor interactions in HCC progression, growth and metastasis and immune response to HCC are reviewed.

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Because spontaneous rupture of hepatocellular carcinoma (HCC) is one kind of bleeding complication related to the blood vessels, the possible mechanism of this rupture should occur on the blood vessel itself. Our hypothesis, which has not yet been investigated, is that the vascular integrity of HCC might be damaged during vascular injury. Design: We examined semiquantitatively the expression of von Willebrand factor, elastin, neutrophil elastase, type IV collagen, and collagenase in 23 specimens of HCC with spontaneous rupture by immunohistochemistry, and compared them with 30 specimens of HCC without rupture. Results: There was a significant decrease of von Willebrand factor, proliferation of degenerated elastin, abnormal distribution of neutrophil elastase, degradation