Legumain promotes fibrogenesis in chronic pancreatitis via activation of transforming growth factor ß1.

Chronic pancreatitis (CP) is a major risk factor for pancreatic cancer; however, little is known about the pathogenic mechanisms underlying the development of CP. Legumain (Lgmn) has been linked to some chronic inflammatory diseases. The present study investigated the role of legumain in pancreatic fibrogenesis. We induced CP in wild type C57BL6 (WT), Lgmn-deficient (Lgmn-/-), Lgmnflox/flox and Lgmnflox/flox × LysMCre mice by intraperitoneal injection of caerulein for 4 weeks. Pancreata were collected and analyzed by quantitative reverse transcription polymerase chain reaction, Western blotting, and histology. Pancreatic stellate cells and macrophages were isolated and studied using immunofluorescence, gelatin zymography, and enzyme-linked immunosorbent assay. The effects of inhibition of legumain were investigated in vivo by administration of the specific legumain inhibitor, RR-11a. Legumain was found to be upregulated in the serum and pancreatic tissues of mice with caerulein-induced CP. Mice with global and macrophage-specific legumain deficiency exhibited significantly reduced development of pancreatic fibrosis compared with control mice, based on pancreas size, histology, and expression of fibrosis-associated genes. Our results indicate that legumain promotes activation of pancreatic stellate cells and increases synthesis of extracellular matrix proteins via activation of matrix metalloproteinase-2(MMP-2), which hydrolyzes the transforming growth factor-ß1 (TGF-ß1) precursor to form active TGF-ß1. Administration of RR-11a markedly attenuated pancreatic fibrosis in mice with CP. Deficiency or inhibition of legumain significantly reduces the severity of pancreatic fibrosis by suppressing activation of the TGF-ß1 precursor. Our results highlight the potential of legumain as a novel therapeutic target for CP. KEY MESSAGES: • Legumain expression was markedly upregulated in CP mice. • Deletion of legumain attenuated pancreatic fibrosis in CP mice. • Legumain promotes fibrosis via MMP-2 activation, which hydrolyzed the TGF-ß1 precursor to the active form. • Legumain is a potential therapeutic target for the management of CP.

Dilation catheter-guided mini-forceps biopsy improves the diagnostic accuracy of malignant biliary strictures.

BACKGROUND: Tissue sampling for biliary stricture is important for differential diagnosis and further treatment. The aim of this study was to assess a novel dilation catheter-guided mini-forceps biopsy (DCMB) method in the diagnosis of malignant biliary strictures. METHODS: 42 patients with malignant biliary stricture who underwent both brush cytology and DCMB during endoscopic retrograde cholangiopancreatography between October 2014 and November 2015 were retrospectively included. During DCMB, the mini biopsy forceps was introduced into the biliary stricture through the dilation catheter, and then the position and direction of the forceps were adjusted to obtain tissue samples. RESULTS: The positive rate of DCMB was significantly higher than that of brush cytology (81.0 % [34/42] vs. 38.1 % [16/42]; P < 0.001). No severe complications occurred; three patients (7.1 %) experienced mild procedure-related acute pancreatitis. CONCLUSIONS: The novel DCMB technique was a practical, safe, efficient, and low-costing method for diagnosing malignant biliary stricture with a high accuracy rate.

Endoscopic ultrasonography-guided drainage combined with trans-duodenoscope cyclic irrigation technique for walled-off pancreatic necrosis.

BACKGROUND: Endoscopic ultrasonography-guided drainage has been established as a good treatment modality in the management of walled-off pancreatic necrosis, but the unmanageable infection of postoperation is still a thorny problem due to the poor drainage ability for solid necrotic debris only through transmural stent and nasocystic catheter. AIMS: Introduce a novel therapeutic method, namely endoscopic ultrasonography-guided drainage combined with cyclic irrigation technique in managing patients with walled-off pancreatic necrosis. METHODS: 18 patients with severe acute pancreatitis complicated with walled-off pancreatic necrosis received treatment with endoscopic ultrasonography-guided drainage combined with cyclic irrigation were involved in this retrospective study. RESULTS: 17 of 18 patients with walled-off pancreatic necrosis were treated by this new therapeutic method. Subsequent surgery was performed in 1 case due to uncontrolled infection, complications such as perforation, bleeding or multiple organ failure were not observed. Treatment success rate was high (16 in 17, 94.12%). CONCLUSION: Endoscopic ultrasonography-guided drainage combined with cyclic irrigation is an effective treatment option for symptomatic walled-off pancreatic necrosis to facilitate drainage and obviate the need for subsequent surgery or endoscopic necrosectomy.