Chemotherapy of Cholangiocarcinoma: Current Management and Future Directions

Cholangiocarcinoma is a relatively rare form of gastroenterological cancer that divided into intrahepatic, perihilar, and distal bile duct cancer. Approximately, 10,000 new cases are diagnosed annually in the United States, and a 5-year survival rate is below 20%. While only surgical resection can provide a cure, most of cholangiocarcinomas are detected at inoperable stage and associated with poor prognosis. Moreover, cholangiocarcinoma has a high recurrence rate, even after curative surgery. Therefore, chemotherapy has an important role in the treatment of patients with cholangiocarcinoma. International efforts by physicians and researchers are revealing genetic factors of cholangiocarcinoma progression, which will identify early diagnostic markers and novel therapeutic targets. In this chapter, current strategies of adjuvant, neoadjuvant, and palliative chemotherapy will be discussed, as well as expectant future therapeutic targets and development of individualized therapies

Photo-patternable and transparent films using cellulose nanofibers for stretchable origami electronics

Substantial progress in flexible or stretchable electronics over the past decade has extensively impacted various technologies such as wearable devices, displays and automotive electronics for smart cars. An important challenge is the reliability of these deformable devices under thermal stress. Different coefficients of thermal expansion (CTE) between plastic substrates and the device components, which include multiple inorganic layers of metals or ceramics, induce thermal stress in the devices during fabrication processes or long-term operations with repetitions of thermal cyclic loading-unloading, leading to device failure and reliability degradation. Here, we report an unconventional approach to form photo-patternable, transparent cellulose nanofiber (CNF) hybrid films as flexible and stretchable substrates to improve device reliability using simultaneous electrospinning and spraying. The electrospun polymeric backbones and sprayed CNF fillers enable the resulting hybrid structure to be photolithographically patternable as a negative photoresist and thermally and mechanically stable, presenting outstanding optical transparency and low CTE. We also formed stretchable origami substrates using the CNF hybrid that are composed of rigid support fixtures and elastomeric joints, exploiting the photo-patternability. A demonstration of transparent organic light-emitting diodes and touchscreen panels on the hybrid film suggests its potential for use in next-generation electronics.ope

Effect of Epigallocatechin-3-Gallate on PMA-Induced MUC5B Expression in Human Airway Epithelial Cells

ObjectivesAmong the inflammatory mediators, phorbol 12-myristate 13-acetate (PMA) is associated with the regulation of MUC5B expression in the airway epithelial cells. Epigallocatechin-3-gallate (EGCG) is the major component of green tea extract. The biological activity of EGCG includes reduction of cholesterol and antioxidant activity, as well as anti-inflammatory effect. However, the precise action mechanism of anti-inflammatory effect of EGCG in the airway epithelial cells has not been fully defined. This study investigates the effect and the brief signaling pathway of EGCG on PMA-induced MUC5B expression in the airway epithelial cells.MethodsIn NCI-H292 airway epithelial cells, the effect and signaling pathway of EGCG on MUC5B expression were investigated using real-time polymerase chain reaction analysis, enzyme immunoassay, immunohistochemical analysis, gelatin zymography assay, and immunoblot analysis.ResultsIn NCI-H292 airway epithelial cells, PMA induced MUC5B expression, phosphorylation of p38 mitogen-activated protein kinase (MAPK), and matrix metalloproteinase-9 (MMP-9) expression and protein activity. EGCG significantly decreased PMA-induced MUC5B expression, phosphorylation of p38 MAPK, and MMP-9 expression and protein activity. SB203580 (p38 MAPK inhibitor) significantly decreased PMA-induced MMP-9 expression. In addition, SB203580 and MMP-9 I (MMP-9 inhibitor) significantly decreased PMA-induced MUC5B expression.ConclusionThese results suggest that EGCG down-regulates PMA-induced MUC5B expression through the p38 MAPK dependent MMP-9 signaling pathway in human airway epithelial cells

Pseudoaneurysm of the Medial Superior Genicular Artery after Arthroscopic Partial Meniscectomy

We describe a case of 43-year-old man who had a pseudoaneurysm of the medial superior genicular artery after arthroscopic partial meniscectomy with standard anterolateral and anteromedial portals. Pseudoaneurysm of the medial superior genicular artery has been reported at the previous superomedial portal site after arthroscopy. Described herein is a unique case that involved the medial superior genicular artery at the previous anteromedial portal site after arthroscopy. The pseudoaneurysm was successfully treated with transcatheter embolization

Endoscopic Papillary Balloon Dilation with Large Balloon after Limited Sphincterotomy for Retrieval of Choledocholithiasis

Endoscopic papillary balloon dilation (EBD) for choledocholithiasis is known to be comparable to endoscopic sphincterotomy (EST) especially in cases of small stones. With larger stones, EBD with conventional balloon, which have a diameter of 6-8 mm, was reported as less effective for extraction of stones. We evaluated the efficacy and complications of EBD with large balloons (10-15 mm) after limited EST for retrieval of choledocholithiasis. From February 2005, we have performed EBD with limited EST for retrieval of common bile duct (CBD) stones. The patients who admitted with hyperamylasemia and gallstone pancreatitis were excluded. In cases without CBD dilation, EPBD with 12 mm for 40 seconds was performed. And in cases with CBD dilation, we dilated the sphincters with 15 mm sized balloon for 40 seconds. Total 22 patients (11 of male) were performed EBD with limited EST for retrieval of CBD stones. The median diameter of the stones was 10 mm (5-25 mm). Ten cases had multiple stones and 6 cases periampullary diverticuli. Successful stone removal in the initial session of ERCP with EBD was accomplished in 16 patients (72.7%). And complete retrieval of bile duct stones was achieved in all patients with repeated ERCP. In the aspect of complications, any episodes of perforation, bleeding was not developed. Only one case of mild grade of post-procedural pancreatitis was noted. However, post-procedural hyperamylasemia was developed in 16 cases (68.2%). EBD with larger balloon seems to be a feasible and safe alternative technique for conventional EST in CBD stone extraction

The T2-Shortening Effect of Gadolinium and the Optimal Conditions for Maximizing the CNR for Evaluating the Biliary System: a Phantom Study

OBJECTIVE: Clear depiction of the common bile duct is important when evaluating neonatal cholestasis in order to differentiate biliary atresia from other diseases. During MR cholangiopancreatography, the T2-shortening effect of gadolinium can increase the contrast-to-noise ratio (CNR) of the bile duct and enhance its depiction. The purpose of this study was to confirm, by performing a phantom study, the T2-shortening effect of gadolinium, to evaluate the effect of different gadolinium chelates with different gadolinium concentrations and different magnetic field strengths for investigating the optimal combination of these conditions, and for identifying the maximum CNR for the evaluation of the biliary system. MATERIALS AND METHODS: MR imaging using a T2-weighted single-shot fast spin echo sequence and T2 relaxometry was performed with a sponge phantom in a syringe tube. Two kinds of contrast agents (Gd-DTPA and Gd-EOB-DTPA) with different gadolinium concentrations were evaluated with 1.5T and 3T scanners. The signal intensities, the CNRs and the T2 relaxation time were analyzed. RESULTS: The signal intensities significantly decreased as the gadolinium concentrations increased (p < 0.001) with both contrast agents. These signal intensities were higher on a 3T (p < 0.001) scanner. The CNRs were higher on a 1.5T (p < 0.001) scanner and they showed no significant change with different gadolinium concentrations. The T2 relaxation time also showed a negative correlation with the gadolinium concentrations (p < 0.001) and the CNRs showed decrease more with Gd-EOB-DTPA (versus Gd-DTPA; p < 0.001) on a 3T scanner (versus 1.5T; p < 0.001). CONCLUSION: A T2-shortening effect of gadolinium exhibits a negative correlation with the gadolinium concentration for both the signal intensities and the T2 relaxation time. A higher CNR can be obtained with Gd-DTPA on a 1.5T MRI scannerope

Epitaxial antiperovskite/perovskite heterostructures for materials design

We demonstrate fabrication of atomically sharp interfaces between nitride antiperovskite Mn$_{3}$GaN and oxide perovskites (La$_{0.3}$Sr$_{0.7}$)(Al$_{0.65}$Ta$_{0.35}$)O$_{3}$ (LSAT) and SrTiO$_{3}$ as paradigms of nitride-antiperovskite/oxide-perovskite heterostructures. Using a combination of scanning transmission electron microscopy (STEM), atomic-resolution spectroscopic techniques, and first-principle calculations, we investigated the atomic-scale structure, composition, and boding at the interface. We show that the epitaxial growth between the antiperovskite and perovskite compounds is mediated by a coherent interfacial monolayer that connects the two anti-structures. We anticipate our results to be a major step for the development of functional antiperovskite/perovskite heterostructures opening to harness a combination of their functional properties including topological properties for ultra low power applications