Grade 3 Pancreatic Neuroendocrine Tumors on MDCT: Establishing a Diagnostic Model and Comparing Survival Against Pancreatic Ductal Adenocarcinoma.

OBJECTIVE. The purpose of this study is to establish a diagnostic model for differentiating grade 3 (G3) pancreatic neuroendocrine tumors (PNETs) from pancreatic ductal adenocarcinomas (PDACs) and to analyze survival outcomes. MATERIALS AND METHODS. Twenty patients with G3 PNETs and 58 patients with PDACs confirmed by surgery or biopsy were retrospectively included. Demographic and radiologic information was collected. Univariate analyses and binary logistic regression analyses were performed to identify independent factors and establish a diagnostic model. An ROC curve was created to determine diagnostic ability. Kaplan-Meier survival analysis was performed. RESULTS. Patients with G3 PNETs were more likely to present with normal carbohydrate antigen (CA) 19-9 levels, normal pancreatic ducts, and round tumors with well-defined margins and higher portal enhancement ratios than were patients with PDAC (p < 0.05). After multivariate analysis, a normal CA 19-9 level (odds ratio, 0.0125; 95% CI, 0.0008-0.2036), round tumor shape (odds ratio, 0.0143; 95% CI, 0.0004-0.5461), and pancreatic duct dilation of 4 mm or less (odds ratio, 17.9804; 95% CI, 1.0098-320.1711) were independent predictors of G3 PNETs. The AUC of the ROC curve was 0.916, and sensitivity and specificity were 90.0% and 81.0%, respectively. Furthermore, patients with G3 PNETs had better overall survival than patients with PDACs. Among patients in the G3 PNET subgroup, patients with liver or lymph node metastases had worse overall survival than patients without metastases. CONCLUSION. A diagnostic model was established to differentiate G3 PNETs from PDACs. A normal CA 19-9 level, round tumor shape, and pancreatic duct dilation of 4 mm or less were factors that were strongly predictive of G3 PNET.

Ultrasound-mediated microbubble delivery of pigment epithelium-derived factor gene into retina inhibits choroidal neovascularization.

BACKGROUND: Many studies have suggested that the imbalance of angiogenic factor and anti-angiogenic factor expression contributes significantly to the development of choroidal neovascularization (CNV), and ultrasound microbubble combination system can increase the gene transfection efficiency successfully. This study was designed to investigate whether ultrasound-mediated microbubble destruction could effectively deliver therapeutic plasmid into the retina of rat, and whether gene transfer of pigment epithelium-derived factor (PEDF) could inhibit CNV. METHODS: Human retinal pigment epithelial cells were isolated and treated either with ultrasound or plasmid alone, or with a combination of plasmid, ultrasound and microbubbles to approach feasibility of microbubble-enhanced ultrasound enhance PEDF gene expression; For in vivo animal studies, CNV was induced by argon lasgon laser in rats. These rats were randomly assigned to five groups and were treated by infusing microbubbles attached with the naked plasmid DNA of PEDF into the vitreous of rats followed by immediate ultrasound exposure (intravitreal injection); infusing liposomes with the naked plasmid DNA of PEDF into the vitreous (lipofectamine + PEDF); infusing microbubbles attached with PEDF into the orbit of rats with ultrasound irradiation immediately (retrobular injection); infusing microbubbles attached with PEDF into the femoral vein of rats with exposed to ultrasound immediately (vein injection). The CNV rats without any treatment served as control. Rats were sacrificed and eyes were enucleated at 7, 14, and 28 days after treatment. Gene and protein expression of PEDF was detected by quantitative real-time RT-PCR, Western blotting and immunofluorescence staining, respectively. The effect of PEDF gene transfer on CNV was examined by fluorescein fundus angiography. RESULTS: In vitro cell experiments showed that microbubbles with ultrasound irradiation could significantly enhance PEDF delivery as compared with microbubbles or ultrasound alone. In the rat CNV model, transfection efficiency mediated by ultrasound/microbubbles was significantly higher than that by lipofectamine-mediated gene transfer at 28 days after treatment. The study also showed that with the administration of ultrasound-mediated microbubbles destruction, the CNV of rats was inhibited effectively. CONCLUSIONS: Ultrasound-microbubble technique could increase PEDF gene transfer into rats' retina and chorioid, in association with a significant inhibition of the development of CNV, suggesting that this noninvasive gene transfer method may provide a useful tool for clinical gene therapy.