Photocrosslinked anhydride systems for long-term protein release.

Injectable delivery systems are attractive as vehicles for localized delivery of therapeutics especially in the context of regenerative medicine. In this study, the potential of photocrosslinked polyanhydride (PA) networks as an encapsulation matrix for long-term delivery of macromolecules was studied. The in vitro release of two model proteins (horseradish peroxidase (HRP) and bovine serum albumin labeled with fluorescein isothiocyanate (FITC-BSA)) was evaluated from crosslinked networks composed of sebacic acid dimethacrylate (MSA), 1,6-bis-carboxyphenoxyhexane dimethacrylate (MCPH), and poly(ethylene glycol) diacrylate (PEGDA), supplemented with calcium carbonate. Prior to incorporation into the networks, proteins were formulated by dilution in a cyclodextrin excipient followed by gelatin-based wet granulation. Protein release was quantified by activity assay (HRP) or fluorescence (FITC-BSA). Each protein was readily released from the networks with a unique release behavior. Most importantly, release of protein with retention of activity was achieved for durations ranging from 1 week to 4 months. The released HRP was additionally visualized using SDS-PAGE. In general, a more hydrophobic network resulted in slower rates of protein release. Incorporation of PEGDA into the matrices was critical for maintenance of integrity during degradation. These results suggest that this system may be useful as an injectable delivery system for long-term delivery of macromolecules.

Clinical and pathologic features influencing survival in patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma.

OBJECTIVE: The aim of the study was to determine the clinicopathological features that influence survival in patients with resected pancreatic ductal adenocarcinoma (PDA). METHODS: The study used a single institution retrospective review of patients undergoing pancreaticoduodenectomy (PD) for PDA from 1993 to 2010. RESULTS: Two hundred forty-six consecutive cases of resected PDA were identified: 128 males (52 %), median age 68 years. Median hospital length of stay was 8 days and 30-day mortality rate was 2.4 %. There were 101 (41.1 %) postoperative complications, 77 % of which were Dindo-Clavien Grade 3 or less. Overall survival was 85, 63, 25, and 15 % at 6 months, 1 year, 3 years, and 5 years, respectively, with a median survival of 17 months. Multivariate Cox proportional hazard modeling demonstrated lymph node ratio was negatively correlated with survival at all time points. Preoperative hypertension was a poor prognostic factor at 6 months, 3 years, and 5 years. The absence of postoperative complications was protective at 6 months whereas pancreatic leaks were associated with worse survival at 6 months. Abdominal pain on presentation, operative time, and estimated blood loss were also associated with decreased survival at various time points. CONCLUSION: The strongest prognostic variable for short- and long-term survival after PD for PDA is lymph node ratio. Short-term survival is influenced by the postoperative course.