Predictive Value of Preoperative Serum CA19-9 on Margin Status.

Serum carbohydrate antigen (CA19-9) is known to correlate with stage, resectability, and prognosis of pancreatic cancer. The goal of pancreaticoduodenectomy is to achieve an R0 resection because worse outcomes are reported in the presence of positive margins. The purpose of this study was to evaluate the predictive utility of CA19-9 for pancreaticoduodenectomy margin status. A retrospective review of patients with pancreatic adenocarcinoma undergoing pancreaticoduodenectomy between October 2007 and November 2018 at our institution was performed. Patient demographics, preoperative CA19-9, and tumor characteristics were analyzed. Univariate and multivariate logistic regression was performed to determine factors associated with positive margins. A total of 184 patients were included. The mean age was 65 years; most patients were male and white. Majority had a positive preoperative CA19-9 (69%). There were nearly twice as many patients with negative as positive margins. Groups had similar demographics and preoperative CA19-9. A greater proportion of patients with negative margins had smaller tumors and early disease. On univariate and multivariate analysis, larger and higher stage tumors had greater odds of positive margins (P < 0.05). There was no significant association between margin status and preoperative CA19-9. Preoperative CA19-9 is not predictive of margin status. These results suggest that although preoperative CA19-9 values are associated with both resectability and prognosis, positive margins may not be a contributing mechanism.

Glycoconjugated Site-Selective DNA-Methylating Agent Targeting Glucose Transporters on Glioma Cells.

DNA-alkylating drugs continue to remain an important weapon in the arsenal against cancers. However, they typically suffer from several shortcomings because of the indiscriminate DNA damage that they cause and their inability to specifically target cancer cells. We have developed a strategy for overcoming the deficiencies in current DNA-alkylating chemotherapy drugs by designing a site-specific DNA-methylating agent that can target cancer cells because of its selective uptake via glucose transporters, which are overexpressed in most cancers. The design features of the molecule, its synthesis, its reactivity with DNA, and its toxicity in human glioblastoma cells are reported here. In this molecule, a glucosamine unit, which can facilitate uptake via glucose transporters, is conjugated to one end of a bispyrrole triamide unit, which is known to bind to the minor groove of DNA at A/T-rich regions. A methyl sulfonate moiety is tethered to the other end of the bispyrrole unit to serve as a DNA-methylating agent. This molecule produces exclusively N3-methyladenine adducts upon reaction with DNA and is an order of magnitude more toxic to treatment resistant human glioblastoma cells than streptozotocin is, a Food and Drug Administration-approved, glycoconjugated DNA-methylating drug. Cellular uptake studies using a fluorescent analogue of our molecule provide evidence of uptake via glucose transporters and localization within the nucleus of cells. These results demonstrate the feasibility of our strategy for developing more potent anticancer chemotherapeutics, while minimizing common side effects resulting from off-target damage.