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Purpose Pancreatic ductal adenocarcinoma (PDA) cells are known to produce excessive amounts of reactive oxygen species (ROS), particularly superoxide, which may contribute to the aggressive and refractory nature of this disease. Extracellular superoxide dismutase (EcSOD) is an antioxidant enzyme that catalyzes the dismutation of superoxide in the extracellular environment. The current work tests the hypothesis that EcSOD modulates PDA growth and invasion by modifying the redox balance in PDA. Experimental Design We evaluated the prognostic significance of EcSOD in a human tissue microarray of patients with PDA. EcSOD overexpression was performed in PDA cell lines and animal models of disease. The impact of EcSOD on PDA cell lines was evaluated with Matrigel invasion in combination with a superoxide-specific SOD mimic and a nitric oxide synthase inhibitor to determine the mechanism of action of EcSOD in PDA. Results Loss of EcSOD expression is a common event in PDA, which correlated with worse disease biology. Overexpression of EcSOD in PDA cell lines resulted in decreased invasiveness that appeared to be related to reactions of superoxide with nitric oxide. Pancreatic cancer xenografts overexpressing EcSOD also demonstrated slower growth and peritoneal metastasis. Over-expression of EcSOD or treatment with a superoxide-specific SOD mimic caused significant decreases in PDA cell invasive capacity. Conclusions These results support the hypothesis that loss of EcSOD leads to increased reactions of superoxide with nitric oxide which contributes to the invasive phenotype. These results allow for the speculation that superoxide dismutase mimetics might inhibit PDA progression in human clinical disease.

Background Data is limited about the robotic platform in rectal dissections, and its use may be perceived as prohibitively expensive or difficult to learn. We report our experience with the initial robotic-assisted rectal dissections performed by a single surgeon, assessing learning curve and cost. Methods Following IRB approval, a retrospective chart review was conducted of the first 85 robotic-assisted rectal dissections performed by a single surgeon between 9/1/2010–12/31/2012. Patient demographic, clinicopathologic, procedure, and outcome data were gathered. Cost data was obtained from the University HealthSystem Consortium (UHC) database. The first 43 cases (Time 1) were compared to the next 42 cases (Time 2) using multivariate linear and logistic regression models. Results Indications for surgery were cancer for 51 patients (60%), inflammatory bowel disease for 18 (21%), and rectal prolapse for 16 (19%). The most common procedures were low anterior resection (n=25, 29%) and abdominoperineal resection (n=21, 25%). The patient body mass index (BMI) was statistically different between the two patient groups (Time 1, 26.1 kg/m2 vs. Time 2, 29.4 kg/m2, p=0.02). Complication and conversion rates did not differ between the groups. Mean operating time was significantly shorter for Time 2 (267 minutes vs. 224 minutes, p=0.049) and remained significant in multivariate analysis. Though not reaching statistical significance, the mean observed direct hospital cost decreased ($17,349 for Time 1 vs. $13,680 for Time 2, p=0.2). The observed/expected cost ratio significantly decreased (1.47 for Time 1 vs. 1.05 for Time 2, p=0.007) but did not remain statistically significant in multivariate analyses. Conclusions Over the series, we demonstrated a significant improvement in operating times. Though not statistically significant, direct hospital costs trended down over time. Studies of larger patient groups are needed to confirm these findings, and to correlate them with procedure volume to better define the learning curve process.

Those treated at hospitals with an NCI designation, residency program, or medical school affiliation received more guideline-concordant care. Initiatives involving provider education and virtual tumor boards may improve care.

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