Prakoso E.,Morrow Gastroenterology and Liver Center |
Prakoso E.,Royal Prince Alfred Hospital |
Thompson J.F.,Sydney Medical School |
Thompson J.F.,University of Sydney |
And 2 more authors.
Gastrointestinal Endoscopy | Year: 2011
Background: Melanoma is the most common tumor to metastasize to the GI tract, where it mainly involves the small bowel. Objective: To compare capsule endoscopy (CE) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT scanning, the current standard and most sensitive investigation modality, in detecting small-bowel metastases in patients with metastatic melanoma. Design: A prospective study of patients with metastatic melanoma who were undergoing FDG PET-CT scanning. CE was performed and the results read by two independent observers without knowledge of the other investigation results. Setting: Tertiary care centers. Patients This study involved 21 patients with a median age of 52 years (range 22-88 years). Intervention CE. Main Outcome Measurements: Detection of small-bowel melanoma. Results FDG PET-CT scanning showed increased abdominal uptake in 12 patients, but only 5 of these patients were found to have small-bowel melanoma on CE. Importantly, in 1 patient with a bleeding small-bowel tumor on CE, the FDG PET-CT scan result was negative. One patient with positive FDG PET-CT scan results and negative CE results subsequently developed symptomatic small-bowel melanoma 10 months after CE. Limitation:s Small-bowel melanoma could not be excluded entirely in 7 patients with positive FDG PET-CT scan results and negative CE results, and follow-up is ongoing. The number of patients in this study was small. Conclusion CE was better than FDG PET-CT scanning in localizing small-bowel melanoma. This study suggests that CE is an ideal complementary investigation modality for patients with known metastatic melanoma undergoing preoperative work-ups and in those with unexplained anemia or GI symptoms. © 2011 American Society for Gastrointestinal Endoscopy.
Seth D.,Royal Prince Alfred Hospital |
Seth D.,University of Sydney |
Duly A.,Garvan Institute |
Kuo P.C.,Loyola University |
And 3 more authors.
World Journal of Gastroenterology | Year: 2014
AIM: To investigate over-expression of Osteopontin (OPN) pathway expression and mechanisms of action in human alcoholic liver disease (ALD), in vivo and in vitro acute alcohol models. METHODS: OPN pathway was evaluated in livers from patients with progressive stages of human ALD and serum from drinkers with and without liver cirrhosis. In vitro stellate LX2 cells exposed to acute alcohol and in vivo in acute alcoholic steatosis mouse models were also investigated for OPN pathway expression and function. WT and OPN-/- mice were administered an acute dose of alcohol and extent of liver injury was examined by histopathology and liver biochemistry after 16-24 h. The causative role of OPN was studied in OPN knockout animals and in vitro in stellate LX2 cells, utilizing siRNA, aptamer and neutralizing antibodies to block OPN and OPN pathway. OPN pathway expression and downstream functional consequences were measured for signaling by Western blotting, plasmin activation by spectrophotometric assays and cell migration by confocal imaging and quantitation. RESULTS: OPN expression positively correlated with disease severity in patients with progressive stages of ALD. In vivo, associated with alcoholic steatosis, a single dose of acute alcohol significantly increased hepatic OPN mRNA and protein, and a cleaved OPN form in a dose dependent manner. OPN mRNA and secreted OPN also increased in parallel with activation of LX2 stellate cells within 4 h of a single dose of alcohol. Expression of OPN receptors, αvβ3-integrin and CD44, increased in human ALD, and in vivo and in vitro with alcohol administration. This was accompanied by downstream phosphorylation of Akt and Erk, increased mRNA expression of several fibrogenesis, fibrinolysis and extracellular matrix pathway genes, plasmin activation and hepatic stellate cell (HSC) migration. Inhibition of OPN and OPN-receptor mediated signaling partially inhibited alcohol-induced HSC activation, plasmin activity and cell migration. CONCLUSION: OPN is a key mediator of the alcohol-induced effects on hepatic stellate cell functions and liver fibrogenesis. © 2014 Baishideng Publishing Group Inc. All rights reserved.